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PMID: 22688817 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Subversion of host recognition and defense systems by Francisella spp.

Microbiology and molecular biology reviews : MMBR ·Vol. 76 ·No. 2 ·2012-06-00 ·Pages 383-404

Jones CL, Napier BA, Sampson TR, Llewellyn AC, Schroeder MR, Weiss DS

Abstract

Francisella tularensis is a gram-negative intracellular pathogen and the causative agent of the disease tularemia. Inhalation of as few as 10 bacteria is sufficient to cause severe disease, making F. tularensis one of the most highly virulent bacterial pathogens. The initial stage of infection is characterized by the "silent" replication of bacteria in the absence of a significant inflammatory response. Francisella achieves this difficult task using several strategies: (i) strong integrity of the bacterial surface to resist host killing mechanisms and the release of inflammatory bacterial components (pathogen-associated molecular patterns [PAMPs]), (ii) modification of PAMPs to prevent activation of inflammatory pathways, and (iii) active modulation of the host response by escaping the phagosome and directly suppressing inflammatory pathways. We review the specific mechanisms by which Francisella achieves these goals to subvert host defenses and promote pathogenesis, highlighting as-yet-unanswered questions and important areas for future study.

MeSH Terms
Animals Francisella tularensis/growth & development,pathogenicity Genome, Bacterial Host-Pathogen Interactions Humans Inflammation Mediators/metabolism Microbial Viability Phagosomes/microbiology Tularemia/microbiology
Chemicals
Inflammation Mediators
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jones Crystal L
Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program, Emory University, Atlanta, Georgia, USA.
Napier Brooke A
Sampson Timothy R
Llewellyn Anna C
Schroeder Max R
Weiss David S
References (242)
242 references, click to expand
  1. Bacterial heme sources: the role of heme, hemoprotein receptors and hemophores.
    Curr Opin Microbiol. 2000 Apr;3(2):215-20 PMID: 10744995
  2. Identification, characterization and immunogenicity of an O-antigen capsular polysaccharide of Francisella tularensis.
    PLoS One. 2010 Jul 06;5(7):e11060 PMID: 20625403
  3. Experimental tularemia in mice challenged by aerosol or intradermally with virulent strains of Francisella tularensis: bacteriologic and histopathologic studies.
    Microb Pathog. 2003 May;34(5):239-48 PMID: 12732472
  4. Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis.
    Eur J Immunol. 2011 Apr;41(4):974-80 PMID: 21442618
  5. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3.
    Nat Immunol. 2005 Apr;6(4):331-7 PMID: 15785758
  6. Diverse myeloid and lymphoid cell subpopulations produce gamma interferon during early innate immune responses to Francisella tularensis live vaccine strain.
    Infect Immun. 2008 Sep;76(9):4311-21 PMID: 18573901
  7. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis.
    Proc Natl Acad Sci U S A. 2010 May 25;107(21):9771-6 PMID: 20457908
  8. Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.
    Cell Microbiol. 2011 Oct;13(10):1586-600 PMID: 21883803
  9. Autophagy, immunity, and microbial adaptations.
    Cell Host Microbe. 2009 Jun 18;5(6):527-49 PMID: 19527881
  10. Macrophage nutriprive antimicrobial mechanisms.
    J Leukoc Biol. 2006 Jun;79(6):1117-28 PMID: 16603587
  11. Development of tolerogenic dendritic cells and regulatory T cells favors exponential bacterial growth and survival during early respiratory tularemia.
    J Leukoc Biol. 2011 Sep;90(3):493-507 PMID: 21724804
  12. Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria.
    J Immunol. 1999 Feb 15;162(4):2291-8 PMID: 9973506
  13. Multiple mechanisms of NADPH oxidase inhibition by type A and type B Francisella tularensis.
    J Leukoc Biol. 2010 Oct;88(4):791-805 PMID: 20610796
  14. Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella.
    Biochem Biophys Res Commun. 2010 May 28;396(2):246-51 PMID: 20399752
  15. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP.
    PLoS Pathog. 2006 Jul;2(7):e71 PMID: 16848641
  16. Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation.
    J Leukoc Biol. 2006 Oct;80(4):766-73 PMID: 16895974
  17. Regulation of iron metabolism in murine J774 macrophages: role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide.
    Blood. 1999 Oct 1;94(7):2383-9 PMID: 10498610
  18. The fslE homolog, FTL_0439 (fupA/B), mediates siderophore-dependent iron uptake in Francisella tularensis LVS.
    Infect Immun. 2010 Oct;78(10):4276-85 PMID: 20696823
  19. Francisella novicida bacteremia, Thailand.
    Emerg Infect Dis. 2008 Dec;14(12):1935-7 PMID: 19046526
  20. Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence.
    Infect Immun. 1994 Sep;62(9):3705-11 PMID: 8063385
  21. The lectin-complement pathway--its role in innate immunity and evolution.
    Immunol Rev. 2004 Apr;198:185-202 PMID: 15199963
  22. Francisella gains a survival advantage within mononuclear phagocytes by suppressing the host IFNgamma response.
    Mol Immunol. 2008 Jul;45(12):3428-37 PMID: 18514317
  23. Host-adaptation of Francisella tularensis alters the bacterium's surface-carbohydrates to hinder effectors of innate and adaptive immunity.
    PLoS One. 2011;6(7):e22335 PMID: 21799828
  24. A Francisella tularensis locus required for spermine responsiveness is necessary for virulence.
    Infect Immun. 2011 Sep;79(9):3665-76 PMID: 21670171
  25. Glutathione provides a source of cysteine essential for intracellular multiplication of Francisella tularensis.
    PLoS Pathog. 2009 Jan;5(1):e1000284 PMID: 19158962
  26. Phagocytosis of leprosy bacilli is mediated by complement receptors CR1 and CR3 on human monocytes and complement component C3 in serum.
    J Clin Invest. 1990 Apr;85(4):1304-14 PMID: 2138634
  27. Identification of Francisella tularensis genes affected by iron limitation.
    Infect Immun. 2006 Jul;74(7):4224-36 PMID: 16790797
  28. Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane.
    J Immunol. 2001 May 1;166(9):5741-8 PMID: 11313417
  29. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
    J Clin Invest. 1998 Feb 15;101(4):890-8 PMID: 9466984
  30. Shigella flexneri: genetics of entry and intercellular dissemination in epithelial cells.
    Curr Top Microbiol Immunol. 1994;192:217-41 PMID: 7859507
  31. Iron content differs between Francisella tularensis subspecies tularensis and subspecies holarctica strains and correlates to their susceptibility to H(2)O(2)-induced killing.
    Infect Immun. 2011 Mar;79(3):1218-24 PMID: 21189323
  32. The role of the complement system in innate immunity.
    Immunol Res. 2005;33(2):103-12 PMID: 16234578
  33. Novel regulatory functions for Toll-like receptor-activated B cells during intracellular bacterial infection.
    Immunol Rev. 2011 Mar;240(1):52-71 PMID: 21349086
  34. Akt-mediated proinflammatory response of mononuclear phagocytes infected with Burkholderia cenocepacia occurs by a novel GSK3β-dependent, IκB kinase-independent mechanism.
    J Immunol. 2011 Jul 15;187(2):635-43 PMID: 21697459
  35. Interferon: a mediator of indoleamine 2,3-dioxygenase induction by lipopolysaccharide, poly(I) X poly(C), and pokeweed mitogen in mouse lung.
    Arch Biochem Biophys. 1986 Sep;249(2):596-604 PMID: 3489442
  36. Interleukin-10 and immunity against prokaryotic and eukaryotic intracellular pathogens.
    Infect Immun. 2011 Aug;79(8):2964-73 PMID: 21576331
  37. Characterization of fig operon mutants of Francisella novicida U112.
    FEMS Microbiol Lett. 2008 Aug;285(2):270-7 PMID: 18564336
  38. Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication.
    Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14578-83 PMID: 16983090
  39. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells.
    Infect Immun. 2005 Apr;73(4):1907-16 PMID: 15784530
  40. TLR4/MyD88/PI3K interactions regulate TLR4 signaling.
    J Leukoc Biol. 2009 Jun;85(6):966-77 PMID: 19289601
  41. Genome-wide identification of Francisella tularensis virulence determinants.
    Infect Immun. 2007 Jun;75(6):3089-101 PMID: 17420240
  42. Francisella tularensis Schu S4 O-antigen and capsule biosynthesis gene mutants induce early cell death in human macrophages.
    Infect Immun. 2011 Feb;79(2):581-94 PMID: 21078861
  43. Phagocytic receptors dictate phagosomal escape and intracellular proliferation of Francisella tularensis.
    Infect Immun. 2011 Jun;79(6):2204-14 PMID: 21422184
  44. Minimal requirements for murine resistance to infection with Francisella tularensis LVS.
    Infect Immun. 1996 Aug;64(8):3288-93 PMID: 8757866
  45. The immunologically distinct O antigens from Francisella tularensis subspecies tularensis and Francisella novicida are both virulence determinants and protective antigens.
    Infect Immun. 2007 Jan;75(1):371-8 PMID: 17074846
  46. LcrV, a substrate for Yersinia enterocolitica type III secretion, is required for toxin targeting into the cytosol of HeLa cells.
    J Biol Chem. 2000 Nov 24;275(47):36869-75 PMID: 10930402
  47. The AcrAB RND efflux system from the live vaccine strain of Francisella tularensis is a multiple drug efflux system that is required for virulence in mice.
    FEMS Microbiol Lett. 2008 Feb;279(2):226-33 PMID: 18179581
  48. Characterization of the siderophore of Francisella tularensis and role of fslA in siderophore production.
    J Bacteriol. 2006 Jun;188(11):3785-95 PMID: 16707671
  49. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides.
    Infect Immun. 2004 Dec;72(12):7107-14 PMID: 15557634
  50. A defined O-antigen polysaccharide mutant of Francisella tularensis live vaccine strain has attenuated virulence while retaining its protective capacity.
    Infect Immun. 2007 May;75(5):2591-602 PMID: 17296751
  51. Francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice.
    Infect Immun. 2009 Nov;77(11):4827-36 PMID: 19703976
  52. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition.
    EMBO Rep. 2004 Oct;5(10):1000-6 PMID: 15359270
  53. In vivo negative selection screen identifies genes required for Francisella virulence.
    Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6037-42 PMID: 17389372
  54. Francisella tularensis induces ubiquitin-dependent major histocompatibility complex class II degradation in activated macrophages.
    Infect Immun. 2009 Nov;77(11):4953-65 PMID: 19703975
  55. Phagocytosis of microorganisms.
    Rev Infect Dis. 1982 Jan-Feb;4(1):104-23 PMID: 6122253
  56. A novel role for B cells in early protective immunity to an intracellular pathogen, Francisella tularensis strain LVS.
    J Immunol. 1997 Apr 1;158(7):3277-84 PMID: 9120284
  57. Francisella tularensis phagosomal escape does not require acidification of the phagosome.
    Infect Immun. 2009 May;77(5):1757-73 PMID: 19237528
  58. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA.
    Nature. 2009 Mar 26;458(7237):509-13 PMID: 19158676
  59. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism.
    FASEB J. 1991 Aug;5(11):2516-22 PMID: 1907934
  60. Nitric oxide-mediated induction of ferritin synthesis in J774 macrophages by inflammatory cytokines: role of selective iron regulatory protein-2 downregulation.
    Blood. 1998 Feb 1;91(3):1059-66 PMID: 9446669
  61. The presence of infectious extracellular Francisella tularensis subsp. novicida in murine plasma after pulmonary challenge.
    Eur J Clin Microbiol Infect Dis. 2008 Apr;27(4):323-5 PMID: 18087734
  62. Deletion of the Bacillus anthracis capB homologue in Francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia.
    J Med Microbiol. 2010 Nov;59(Pt 11):1275-1284 PMID: 20651039
  63. Macrophage replication screen identifies a novel Francisella hydroperoxide resistance protein involved in virulence.
    PLoS One. 2011;6(9):e24201 PMID: 21915295
  64. Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection.
    Immunity. 2010 Nov 24;33(5):777-90 PMID: 21093317
  65. Attenuation and protective efficacy of an O-antigen-deficient mutant of Francisella tularensis LVS.
    Microbiology (Reading). 2007 Sep;153(Pt 9):3141-3153 PMID: 17768257
  66. Type I interferon signaling is required for activation of the inflammasome during Francisella infection.
    J Exp Med. 2007 May 14;204(5):987-94 PMID: 17452523
  67. A tolC mutant of Francisella tularensis is hypercytotoxic compared to the wild type and elicits increased proinflammatory responses from host cells.
    Infect Immun. 2010 Mar;78(3):1022-31 PMID: 20028804
  68. AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium DT104.
    Antimicrob Agents Chemother. 2004 Oct;48(10):3729-35 PMID: 15388427
  69. The inflammasomes: guardians of the body.
    Annu Rev Immunol. 2009;27:229-65 PMID: 19302040
  70. Structure and biosynthesis of free lipid A molecules that replace lipopolysaccharide in Francisella tularensis subsp. novicida.
    Biochemistry. 2006 Dec 5;45(48):14427-40 PMID: 17128982
  71. Siderophore-based iron acquisition and pathogen control.
    Microbiol Mol Biol Rev. 2007 Sep;71(3):413-51 PMID: 17804665
  72. Francisella infections in farmed and wild aquatic organisms.
    Vet Res. 2011 Mar 08;42:47 PMID: 21385413
  73. Differential infection of mononuclear phagocytes by Francisella tularensis: role of the macrophage mannose receptor.
    J Leukoc Biol. 2006 Sep;80(3):563-71 PMID: 16816147
  74. Phagocytosis of microbes: complexity in action.
    Annu Rev Immunol. 2002;20:825-52 PMID: 11861619
  75. Antimicrobial activity of human beta-defensins and induction by Francisella.
    Biochem Biophys Res Commun. 2008 Jul 11;371(4):670-4 PMID: 18452706
  76. Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape.
    J Leukoc Biol. 2006 Dec;80(6):1224-30 PMID: 16908516
  77. Infected-host-cell repertoire and cellular response in the lung following inhalation of Francisella tularensis Schu S4, LVS, or U112.
    Infect Immun. 2008 Dec;76(12):5843-52 PMID: 18852251
  78. Modulation of p47PHOX activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase.
    Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5130-5 PMID: 12704229
  79. The complete genome sequence of Francisella tularensis, the causative agent of tularemia.
    Nat Genet. 2005 Feb;37(2):153-9 PMID: 15640799
  80. The respiratory burst-inhibiting acid phosphatase AcpA is not essential for the intramacrophage growth or virulence of Francisella novicida.
    FEMS Microbiol Lett. 1999 Jul 1;176(1):85-90 PMID: 10418134
  81. Antimicrobial peptides important in innate immunity.
    FEBS J. 2011 Oct;278(20):3942-51 PMID: 21848912
  82. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system.
    Microbiology (Reading). 1995 Mar;141 ( Pt 3):611-22 PMID: 7711899
  83. A Francisella mutant in lipid A carbohydrate modification elicits protective immunity.
    PLoS Pathog. 2008 Feb 8;4(2):e24 PMID: 18266468
  84. TLR2 signaling contributes to rapid inflammasome activation during F. novicida infection.
    PLoS One. 2011;6(6):e20609 PMID: 21698237
  85. IFN-gamma represses IL-4 expression via IRF-1 and IRF-2.
    Immunity. 2002 Dec;17(6):703-12 PMID: 12479817
  86. In vivo modulation of the murine immune response to Francisella tularensis LVS by administration of anticytokine antibodies.
    Infect Immun. 1992 Jan;60(1):84-9 PMID: 1729199
  87. Cryopyrin activates the inflammasome in response to toxins and ATP.
    Nature. 2006 Mar 9;440(7081):228-32 PMID: 16407890
  88. Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS.
    Int Immunol. 2006 May;18(5):785-95 PMID: 16574669
  89. Restricted cytosolic growth of Francisella tularensis subsp. tularensis by IFN-gamma activation of macrophages.
    Microbiology (Reading). 2010 Feb;156(Pt 2):327-339 PMID: 19926654
  90. O antigen and lipid A phosphoryl groups in resistance of Salmonella typhimurium LT-2 to nonoxidative killing in human polymorphonuclear neutrophils.
    Infect Immun. 1989 Dec;57(12):3894-900 PMID: 2478480
  91. Transcriptional profiling of host responses in mouse lungs following aerosol infection with type A Francisella tularensis.
    J Med Microbiol. 2006 Mar;55(Pt 3):263-271 PMID: 16476789
  92. Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection.
    Am J Respir Crit Care Med. 2002 Apr 1;165(7):992-5 PMID: 11934727
  93. Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity.
    Nature. 2011 Aug 28;477(7366):592-5 PMID: 21874021
  94. The Francisella pathogenicity island protein IglA localizes to the bacterial cytoplasm and is needed for intracellular growth.
    BMC Microbiol. 2007 Jan 17;7:1 PMID: 17233889
  95. The leukocyte NADPH oxidase.
    Isr Med Assoc J. 2002 Nov;4(11):1023-4 PMID: 12489496
  96. Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria.
    J Leukoc Biol. 2006 Oct;80(4):774-86 PMID: 16857732
  97. Interaction of B cells with intracellular pathogen Francisella tularensis.
    Microb Pathog. 2008 Aug;45(2):79-85 PMID: 18524531
  98. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
    Nat Immunol. 2010 May;11(5):373-84 PMID: 20404851
  99. Innate immune recognition.
    Annu Rev Immunol. 2002;20:197-216 PMID: 11861602
  100. The early phagosomal stage of Francisella tularensis determines optimal phagosomal escape and Francisella pathogenicity island protein expression.
    Infect Immun. 2008 Dec;76(12):5488-99 PMID: 18852245
  101. Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release.
    J Immunol. 2005 Mar 15;174(6):3658-67 PMID: 15749904
  102. Iron uptake mechanisms and their regulation in pathogenic bacteria.
    Int J Med Microbiol. 2001 May;291(2):67-79 PMID: 11437341
  103. Phosphatidylinositol 3-kinase activation attenuates the TLR2-mediated macrophage proinflammatory cytokine response to Francisella tularensis live vaccine strain.
    J Immunol. 2010 Dec 15;185(12):7562-72 PMID: 21098227
  104. The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm.
    Cell Microbiol. 2005 Jul;7(7):969-79 PMID: 15953029
  105. A new view of prostaglandin E regulation of the immune response.
    Immunol Today. 1991 Oct;12(10):349-52 PMID: 1958288
  106. Francisella tularensis enters macrophages via a novel process involving pseudopod loops.
    Infect Immun. 2005 Sep;73(9):5892-902 PMID: 16113308
  107. Superoxide dismutase B gene (sodB)-deficient mutants of Francisella tularensis demonstrate hypersensitivity to oxidative stress and attenuated virulence.
    J Bacteriol. 2006 Sep;188(17):6443-8 PMID: 16923916
  108. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses.
    Nat Immunol. 2010 May;11(5):395-402 PMID: 20351692
  109. A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine.
    Infect Immun. 2005 Dec;73(12):8345-52 PMID: 16299332
  110. A Francisella tularensis live vaccine strain (LVS) mutant with a deletion in capB, encoding a putative capsular biosynthesis protein, is significantly more attenuated than LVS yet induces potent protective immunity in mice against F. tularensis challenge.
    Infect Immun. 2010 Oct;78(10):4341-55 PMID: 20643859
  111. The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion.
    Microbiology (Reading). 2011 Dec;157(Pt 12):3483-3491 PMID: 21980115
  112. Direct and indirect impairment of human dendritic cell function by virulent Francisella tularensis Schu S4.
    Infect Immun. 2009 Jan;77(1):180-95 PMID: 18981246
  113. A novel role for plasmin-mediated degradation of opsonizing antibody in the evasion of host immunity by virulent, but not attenuated, Francisella tularensis.
    J Immunol. 2009 Oct 1;183(7):4593-600 PMID: 19752236
  114. The binding of human plasminogen to fibrin and fibrinogen.
    J Biol Chem. 1983 Apr 10;258(7):4249-56 PMID: 6833255
  115. Subversion of complement activation at the bacterial surface promotes serum resistance and opsonophagocytosis of Francisella tularensis.
    J Leukoc Biol. 2008 Jul;84(1):77-85 PMID: 18430786
  116. Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax.
    EMBO J. 2005 Jan 12;24(1):221-7 PMID: 15616593
  117. Toll-like receptor 4 (TLR4) does not confer a resistance advantage on mice against low-dose aerosol infection with virulent type A Francisella tularensis.
    Microb Pathog. 2004 Oct;37(4):185-91 PMID: 15458779
  118. Modulation of biogenesis of the Francisella tularensis subsp. novicida-containing phagosome in quiescent human macrophages and its maturation into a phagolysosome upon activation by IFN-gamma.
    Cell Microbiol. 2005 Jul;7(7):957-67 PMID: 15953028
  119. Francisella novicida LPS has greater immunobiological activity in mice than F. tularensis LPS, and contributes to F. novicida murine pathogenesis.
    Microbes Infect. 2003 Apr;5(5):397-403 PMID: 12737995
  120. Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuole and plasmid-mediated contact hemolysis.
    Infect Immun. 1986 Feb;51(2):461-9 PMID: 3510976
  121. Active suppression of the pulmonary immune response by Francisella tularensis Schu4.
    J Immunol. 2007 Apr 1;178(7):4538-47 PMID: 17372012
  122. The 58-kilodalton major virulence factor of Francisella tularensis is required for efficient utilization of iron.
    Infect Immun. 2009 Oct;77(10):4429-36 PMID: 19651867
  123. The protein secretion systems in Listeria: inside out bacterial virulence.
    FEMS Microbiol Rev. 2006 Sep;30(5):774-805 PMID: 16911044
  124. The yin and yang of type I interferon activity in bacterial infection.
    Nat Rev Immunol. 2005 Sep;5(9):675-87 PMID: 16110316
  125. Some Features of the Squirrel Plague Problem.
    Cal State J Med. 1911 Mar;9(3):105-9 PMID: 18735187
  126. Francisella tularensis subsp. novicida isolated from a human in Arizona.
    BMC Res Notes. 2009 Nov 06;2:223 PMID: 19895698
  127. Francisella tularensis-infected macrophages release prostaglandin E2 that blocks T cell proliferation and promotes a Th2-like response.
    J Immunol. 2007 Feb 15;178(4):2065-74 PMID: 17277110
  128. Characterization and sequencing of a respiratory burst-inhibiting acid phosphatase from Francisella tularensis.
    J Biol Chem. 1996 May 3;271(18):10973-83 PMID: 8631917
  129. In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70.
    Infect Immun. 2002 Apr;70(4):1936-48 PMID: 11895957
  130. IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways.
    EMBO J. 1998 Feb 16;17(4):1006-18 PMID: 9463379
  131. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.
    Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3076-80 PMID: 20133635
  132. Francisella tularensis uses cholesterol and clathrin-based endocytic mechanisms to invade hepatocytes.
    Sci Rep. 2011;1:192 PMID: 22355707
  133. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis.
    Nat Immunol. 2010 May;11(5):385-93 PMID: 20351693
  134. Francisella inhibits STAT1-mediated signaling in macrophages and prevents activation of antigen-specific T cells.
    Int Immunol. 2009 Jan;21(1):19-28 PMID: 19001470
  135. Discovery of new biosynthetic pathways: the lipid A story.
    J Lipid Res. 2009 Apr;50 Suppl:S103-8 PMID: 18974037
  136. The effects of Francisella tularensis infection on iron metabolism in man.
    Am J Med Sci. 1969 Jul;258(1):14-25 PMID: 4894492
  137. TolC, an Escherichia coli outer membrane protein required for hemolysin secretion.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4776-80 PMID: 2112747
  138. Characterization of the receptor-ligand pathways important for entry and survival of Francisella tularensis in human macrophages.
    Infect Immun. 2006 Sep;74(9):5114-25 PMID: 16926403
  139. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis.
    J Exp Med. 2005 Oct 3;202(7):987-99 PMID: 16203868
  140. Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors.
    Infect Immun. 2006 Dec;74(12):6730-8 PMID: 16982824
  141. Francisella tularensis has a significant extracellular phase in infected mice.
    J Infect Dis. 2007 Jul 1;196(1):134-7 PMID: 17538893
  142. The structure and function of Francisella lipopolysaccharide.
    Ann N Y Acad Sci. 2007 Jun;1105:202-18 PMID: 17395723
  143. The Francisella pathogenicity island.
    Ann N Y Acad Sci. 2007 Jun;1105:122-37 PMID: 17395722
  144. Combined deletion of four Francisella novicida acid phosphatases attenuates virulence and macrophage vacuolar escape.
    Infect Immun. 2008 Aug;76(8):3690-9 PMID: 18490464
  145. A novel receptor - ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu.
    BMC Microbiol. 2008 Sep 12;8:145 PMID: 18789156
  146. Alternative activation of macrophages: mechanism and functions.
    Immunity. 2010 May 28;32(5):593-604 PMID: 20510870
  147. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC.
    Nature. 2009 Mar 26;458(7237):514-8 PMID: 19158675
  148. Akt and SHIP modulate Francisella escape from the phagosome and induction of the Fas-mediated death pathway.
    PLoS One. 2009 Nov 20;4(11):e7919 PMID: 19936232
  149. Evasion of IFN-γ signaling by Francisella novicida is dependent upon Francisella outer membrane protein C.
    PLoS One. 2011 Mar 31;6(3):e18201 PMID: 21483828
  150. Francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production.
    J Biol Chem. 2010 Sep 3;285(36):27553-60 PMID: 20558723
  151. Binding and Cellular Activation Studies Reveal That Toll-like Receptor 2 Can Differentially Recognize Peptidoglycan from Gram-positive and Gram-negative Bacteria.
    J Biol Chem. 2009 Mar 27;284(13):8643-53 PMID: 19164296
  152. Toll-like receptor 2-mediated signaling requirements for Francisella tularensis live vaccine strain infection of murine macrophages.
    Infect Immun. 2007 Aug;75(8):4127-37 PMID: 17517865
  153. TLR-dependent control of Francisella tularensis infection and host inflammatory responses.
    PLoS One. 2009 Nov 20;4(11):e7920 PMID: 19936231
  154. Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fc gamma receptor-mediated phagocytosis.
    J Cell Biol. 2001 Jun 25;153(7):1369-80 PMID: 11425868
  155. The immune response against Francisella tularensis live vaccine strain in Lps(n) and Lps(d) mice.
    FEMS Immunol Med Microbiol. 1996 Mar;13(3):235-8 PMID: 8861035
  156. Attenuated virulence of a Francisella mutant lacking the lipid A 4'-phosphatase.
    Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4136-41 PMID: 17360489
  157. Interferon-gamma: an overview of signals, mechanisms and functions.
    J Leukoc Biol. 2004 Feb;75(2):163-89 PMID: 14525967
  158. Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia.
    Eur Respir J. 2006 Feb;27(2):253-60 PMID: 16452577
  159. Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation.
    Infect Immun. 2005 Aug;73(8):5212-6 PMID: 16041042
  160. A variety of novel lipid A structures obtained from Francisella tularensis live vaccine strain.
    Innate Immun. 2012 Apr;18(2):268-78 PMID: 21709054
  161. Deletion of TolC orthologs in Francisella tularensis identifies roles in multidrug resistance and virulence.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12897-902 PMID: 16908853
  162. Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis.
    J Exp Med. 2005 Oct 17;202(8):1043-9 PMID: 16230474
  163. Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection.
    Infect Immun. 1994 Jul;62(7):2779-83 PMID: 8005668
  164. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity.
    Nature. 2009 Oct 8;461(7265):788-92 PMID: 19776740
  165. Toll-like receptor 4 (TLR4) plays a relatively minor role in murine defense against primary intradermal infection with Francisella tularensis LVS.
    Immunol Lett. 2005 Feb 15;97(1):151-4 PMID: 15626487
  166. Identification of Francisella tularensis live vaccine strain CuZn superoxide dismutase as critical for resistance to extracellularly generated reactive oxygen species.
    J Bacteriol. 2009 Oct;191(20):6447-56 PMID: 19684141
  167. Detection of Francisella tularensis in blood by polymerase chain reaction.
    J Clin Microbiol. 1993 Jan;31(1):152-4 PMID: 8417022
  168. A conserved and immunodominant lipoprotein of Francisella tularensis is proinflammatory but not essential for virulence.
    Microb Pathog. 2008 Jun;44(6):512-23 PMID: 18304778
  169. Life on the inside: the intracellular lifestyle of cytosolic bacteria.
    Nat Rev Microbiol. 2009 May;7(5):333-40 PMID: 19369949
  170. Francisella tularensis strain LVS resides in MHC II-positive autophagic vacuoles in macrophages.
    Folia Microbiol (Praha). 2007;52(6):631-6 PMID: 18450226
  171. An attenuated strain of the facultative intracellular bacterium Francisella tularensis can escape the phagosome of monocytic cells.
    Infect Immun. 2003 Oct;71(10):5940-50 PMID: 14500514
  172. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations.
    Ann N Y Acad Sci. 2007 Jun;1105:1-29 PMID: 17395726
  173. A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system.
    Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):997-1002 PMID: 17215377
  174. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3.
    J Immunol. 1990 Apr 1;144(7):2771-80 PMID: 2108212
  175. Resistance of Francisella tularensis strains against reactive nitrogen and oxygen species with special reference to the role of KatG.
    Infect Immun. 2007 Mar;75(3):1303-9 PMID: 17210667
  176. The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence.
    Mol Microbiol. 2009 Dec;74(6):1459-70 PMID: 20054881
  177. The capBCA Locus is Required for Intracellular Growth of Francisella tularensis LVS.
    Front Microbiol. 2011 Apr 25;2:83 PMID: 21747799
  178. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon.
    J Bacteriol. 1993 Nov;175(22):7363-72 PMID: 8226684
  179. Double mechanism for apical tryptophan depletion in polarized human bronchial epithelium.
    J Immunol. 2004 Jul 1;173(1):542-9 PMID: 15210815
  180. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA.
    Science. 2009 Feb 20;323(5917):1057-60 PMID: 19131592
  181. Cellular responses to interferon-gamma.
    Annu Rev Immunol. 1997;15:749-95 PMID: 9143706
  182. Francisella tularensis resistance to bactericidal action of normal human serum.
    FEMS Immunol Med Microbiol. 1996 Mar;13(3):249-52 PMID: 8861038
  183. IFN-β mediates suppression of IL-12p40 in human dendritic cells following infection with virulent Francisella tularensis.
    J Immunol. 2011 Aug 15;187(4):1845-55 PMID: 21753150
  184. Francisella tularensis induces cytopathogenicity and apoptosis in murine macrophages via a mechanism that requires intracellular bacterial multiplication.
    Infect Immun. 2001 Jul;69(7):4691-4 PMID: 11402018
  185. Francisella tularensis induces aberrant activation of pulmonary dendritic cells.
    J Immunol. 2005 Nov 15;175(10):6792-801 PMID: 16272336
  186. Autophagy in immunity and inflammation.
    Nature. 2011 Jan 20;469(7330):323-35 PMID: 21248839
  187. Global transcriptional response to spermine, a component of the intramacrophage environment, reveals regulation of Francisella gene expression through insertion sequence elements.
    J Bacteriol. 2009 Nov;191(22):6855-64 PMID: 19749055
  188. Francisella tularensis inhibits Toll-like receptor-mediated activation of intracellular signalling and secretion of TNF-alpha and IL-1 from murine macrophages.
    Cell Microbiol. 2003 Jan;5(1):41-51 PMID: 12542469
  189. TLR signaling pathways.
    Semin Immunol. 2004 Feb;16(1):3-9 PMID: 14751757
  190. Myeloid differentiation factor-88 (MyD88) is essential for control of primary in vivo Francisella tularensis LVS infection, but not for control of intra-macrophage bacterial replication.
    Microbes Infect. 2006 Mar;8(3):779-90 PMID: 16513388
  191. Microarray analysis of human monocytes infected with Francisella tularensis identifies new targets of host response subversion.
    PLoS One. 2008 Aug 13;3(8):e2924 PMID: 18698339
  192. Immature, but not inactive: the tolerogenic function of immature dendritic cells.
    Immunol Cell Biol. 2002 Oct;80(5):477-83 PMID: 12225384
  193. Inability of the Francisella tularensis lipopolysaccharide to mimic or to antagonize the induction of cell activation by endotoxins.
    Infect Immun. 1996 Jun;64(6):2041-6 PMID: 8675305
  194. IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways.
    J Biol Chem. 2006 Apr 14;281(15):10073-80 PMID: 16484229
  195. Acid phosphatases do not contribute to the pathogenesis of type A Francisella tularensis.
    Infect Immun. 2010 Jan;78(1):59-67 PMID: 19858304
  196. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.
    Science. 2004 Dec 17;306(5704):2090-3 PMID: 15514116
  197. fslE is necessary for siderophore-mediated iron acquisition in Francisella tularensis Schu S4.
    J Bacteriol. 2008 Aug;190(15):5353-61 PMID: 18539739
  198. Francisella tularensis genes required for inhibition of the neutrophil respiratory burst and intramacrophage growth identified by random transposon mutagenesis of strain LVS.
    Infect Immun. 2009 Apr;77(4):1324-36 PMID: 19204089
  199. Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies.
    PLoS Pathog. 2009 May;5(5):e1000459 PMID: 19478886
  200. Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2/TLR1 heterodimer.
    J Biol Chem. 2008 Feb 15;283(7):3751-60 PMID: 18079113
  201. Evasion of complement-mediated lysis and complement C3 deposition are regulated by Francisella tularensis lipopolysaccharide O antigen.
    J Immunol. 2008 Oct 15;181(8):5568-78 PMID: 18832715
  202. Binding and activation of host plasminogen on the surface of Francisella tularensis.
    BMC Microbiol. 2010 Mar 12;10:76 PMID: 20226053
  203. Construction and characterization of an attenuated purine auxotroph in a Francisella tularensis live vaccine strain.
    Infect Immun. 2006 Aug;74(8):4452-61 PMID: 16861631
  204. Induction of pulmonary indoleamine 2,3-dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide.
    Proc Natl Acad Sci U S A. 1978 Aug;75(8):3998-4000 PMID: 279015
  205. Molecular complexity orchestrates modulation of phagosome biogenesis and escape to the cytosol of macrophages by Francisella tularensis.
    Environ Microbiol. 2010 Sep;12(9):2559-86 PMID: 20482590
  206. Acquisition of the vacuolar ATPase proton pump and phagosome acidification are essential for escape of Francisella tularensis into the macrophage cytosol.
    Infect Immun. 2008 Jun;76(6):2671-7 PMID: 18390995
  207. Identification of Burkholderia pseudomallei genes required for the intracellular life cycle and in vivo virulence.
    Infect Immun. 2006 Jun;74(6):3576-86 PMID: 16714590
  208. Feo--transport of ferrous iron into bacteria.
    Biometals. 2006 Apr;19(2):143-57 PMID: 16718600
  209. Uptake of serum-opsonized Francisella tularensis by macrophages can be mediated by class A scavenger receptors.
    Cell Microbiol. 2006 Aug;8(8):1361-70 PMID: 16882038
  210. Nod-like receptors: sentinels at host membranes.
    Curr Opin Immunol. 2010 Aug;22(4):428-34 PMID: 20605429
  211. pH-dependent perforation of macrophage phagosomes by listeriolysin O from Listeria monocytogenes.
    J Exp Med. 1997 Oct 6;186(7):1159-63 PMID: 9314564
  212. Francisella tularensis regulates autophagy-related host cell signaling pathways.
    Autophagy. 2009 Jan;5(1):125-8 PMID: 19029814
  213. The role of complement opsonization in interactions between F. tularensis subsp. novicida and human neutrophils.
    Microbes Infect. 2009 Jul-Aug;11(8-9):762-9 PMID: 19409509
  214. Functional organization and nucleotide sequence of virulence Region-2 on the large virulence plasmid in Shigella flexneri 2a.
    Mol Microbiol. 1989 Sep;3(9):1191-201 PMID: 2552264
  215. Phagocytosis of the Legionnaires' disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil.
    Cell. 1984 Jan;36(1):27-33 PMID: 6692469
  216. A capsule-deficient mutant of Francisella tularensis LVS exhibits enhanced sensitivity to killing by serum but diminished sensitivity to killing by polymorphonuclear leukocytes.
    Infect Immun. 1988 May;56(5):1194-202 PMID: 3356465
  217. Factors affecting the escape of Francisella tularensis from the phagolysosome.
    J Med Microbiol. 2004 Oct;53(Pt 10):953-958 PMID: 15358816
  218. Iron and susceptibility to infectious disease.
    Science. 1974 May 31;184(4140):952-6 PMID: 4596821
  219. Inhibition of complement-mediated opsonization and phagocytosis of Streptococcus pyogenes by D fragments of fibrinogen and fibrin bound to cell surface M protein.
    J Exp Med. 1985 Dec 1;162(6):1983-97 PMID: 3906018
  220. Assembly of the phagocyte NADPH oxidase.
    Histochem Cell Biol. 2004 Oct;122(4):277-91 PMID: 15293055
  221. Isolation and mutagenesis of a capsule-like complex (CLC) from Francisella tularensis, and contribution of the CLC to F. tularensis virulence in mice.
    PLoS One. 2011 Apr 22;6(4):e19003 PMID: 21544194
  222. Induction of type I interferons by bacteria.
    Cell Microbiol. 2010 Jul;12(7):881-90 PMID: 20482555
  223. Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis.
    J Immunol. 2010 Nov 1;185(9):5476-85 PMID: 20921527
  224. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction.
    Nat Immunol. 2012 Jan 29;13(3):255-63 PMID: 22286270
  225. Influence of genetic background on host resistance to experimental murine tularemia.
    Infect Immun. 1988 Aug;56(8):2089-93 PMID: 3397185
  226. Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens.
    BMC Microbiol. 2010 Feb 25;10:64 PMID: 20184753
  227. Tryptophan prototrophy contributes to Francisella tularensis evasion of gamma interferon-mediated host defense.
    Infect Immun. 2011 Jun;79(6):2356-61 PMID: 21464086
  228. Francisella tularensis reveals a disparity between human and mouse NLRP3 inflammasome activation.
    J Biol Chem. 2011 Nov 11;286(45):39033-42 PMID: 21930705
  229. Francisella targets cholesterol-rich host cell membrane domains for entry into macrophages.
    J Immunol. 2008 Jun 15;180(12):8262-71 PMID: 18523292
  230. An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain.
    Vaccine. 2008 Sep 26;26(41):5276-88 PMID: 18692537
  231. Francisella-arthropod vector interaction and its role in patho-adaptation to infect mammals.
    Front Microbiol. 2011 Feb 18;2:34 PMID: 21687425
  232. Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism.
    J Immunol. 2008 Sep 15;181(6):4159-67 PMID: 18768873
  233. Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa.
    J Exp Med. 2002 Jul 1;196(1):109-18 PMID: 12093875
  234. Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.
    Genome Biol. 2007;8(6):R102 PMID: 17550600
  235. Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression.
    J Exp Med. 2002 Oct 21;196(8):1017-24 PMID: 12391013
  236. A two-component Kdo hydrolase in the inner membrane of Francisella novicida.
    Mol Microbiol. 2010 Nov;78(4):820-36 PMID: 20662782
  237. Autophagy genes in immunity.
    Nat Immunol. 2009 May;10(5):461-70 PMID: 19381141
  238. Francisella acid phosphatases inactivate the NADPH oxidase in human phagocytes.
    J Immunol. 2010 May 1;184(9):5141-50 PMID: 20348422
  239. Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence.
    J Immunol. 2010 Sep 1;185(5):2670-4 PMID: 20679532
  240. Indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs.
    Infect Immun. 2010 Jun;78(6):2723-33 PMID: 20385761
  241. Francisella tularensis metabolism and its relation to virulence.
    Front Microbiol. 2010 Dec 24;1:140 PMID: 21687763
  242. Identification of Francisella tularensis Himar1-based transposon mutants defective for replication in macrophages.
    Infect Immun. 2007 Nov;75(11):5376-89 PMID: 17682043
Article Info
Journal
Microbiology and molecular biology reviews : MMBR
Abbr.
Microbiol Mol Biol Rev
ISSN
1098-5557
DOI
10.1128/MMBR.05027-11
Published
2012-06-00
Pages
383-404
Language
English
Region
United States
NLM ID
9706653
PMCID
PMC3372254
Subset
IM
Grants
NIAID NIH HHS · R56 AI087673 · United States
NIAID NIH HHS · U54 AI057157 · United States
NIAID NIH HHS · U54-AI057157 · United States
NIAID NIH HHS · R56-AI087673 · United States
External Links
PubMed source DOI: 10.1128/MMBR.05027-11 PMC Full Text View journal details
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