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PMID: 9573248 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Role of interleukin-12 in primary influenza virus infection.

Journal of virology ·Vol. 72 ·No. 6 ·1998-06-00 ·Pages 4825-31

Monteiro JM, Harvey C, Trinchieri G

Abstract

The effect of endogenous interleukin-12 (IL-12) on the influenza virus immune response in BALB/c mice was evaluated. Following primary influenza virus infection, IL-12 mRNA and protein are detected in the lung, with live virus being required for cytokine induction. Endogenous IL-12 contributes to early NK cell-dependent gamma interferon (IFN-gamma) production (days 3 and 5) but not late T-cell-dependent IFN-gamma secretion (day 7). IL-12 contributes to the inhibition of early virus replication but is not required for virus clearance. IL-12 also modestly contributes to the activation of cytotoxic T lymphocytes. Thus, in this model of experimental influenza virus infection, endogenous IL-12 contributes primarily to the early development and activation of the innate immune response.

MeSH Terms
Animals Female Immunity Interleukin-12/biosynthesis,immunology Killer Cells, Natural/immunology Mice Mice, Inbred BALB C Orthomyxoviridae/immunology Orthomyxoviridae Infections/immunology RNA, Messenger/analysis
Chemicals
RNA, Messenger Interleukin-12
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Monteiro J M
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA.
Harvey C
Trinchieri G
References (52)
52 references, click to expand
  1. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.
    J Exp Med. 1989 Sep 1;170(3):827-45 PMID: 2504877
  2. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells.
    Proc Natl Acad Sci U S A. 1982 May;79(10):3082-6 PMID: 6179076
  3. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages.
    Science. 1993 Apr 23;260(5107):547-9 PMID: 8097338
  4. Response to influenza infection in mice with a targeted disruption in the interferon gamma gene.
    J Exp Med. 1993 Nov 1;178(5):1725-32 PMID: 8228818
  5. Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF.
    J Exp Med. 1992 Mar 1;175(3):779-88 PMID: 1346796
  6. Passive transfer of local immunity to influenza virus infection by IgA antibody.
    J Immunol. 1991 Mar 15;146(6):1972-8 PMID: 2005388
  7. Mechanism of recovery from acute virus infection. VIII. Treatment of lymphocytic choriomeningitis virus-infected mice with anti-interferon-gamma monoclonal antibody blocks generation of virus-specific cytotoxic T lymphocytes and virus elimination.
    Eur J Immunol. 1989 Jul;19(7):1283-8 PMID: 2503388
  8. In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection.
    J Immunol. 1986 Feb 15;136(4):1435-41 PMID: 3944461
  9. Influenza-specific antibody-secreting cells and B cell memory in the murine lung after immunization with wild-type, cold-adapted variant and inactivated influenza viruses.
    Vaccine. 1987 Sep;5(3):244-8 PMID: 3499714
  10. Herpes simplex virus type 1-mediated up-regulation of IL-12 (p40) mRNA expression. Implications in immunopathogenesis and protection.
    J Immunol. 1996 Feb 1;156(3):1110-6 PMID: 8557986
  11. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.
    J Exp Med. 1992 Nov 1;176(5):1387-98 PMID: 1357073
  12. Mechanism of interleukin 12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids.
    J Exp Med. 1995 Mar 1;181(3):901-14 PMID: 7869050
  13. Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin.
    Eur J Immunol. 1984 Jan;14(1):52-6 PMID: 6420170
  14. IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones.
    J Immunol. 1996 Mar 1;156(5):1748-55 PMID: 8596023
  15. Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity.
    J Immunol. 1995 Jan 1;154(1):116-27 PMID: 7527811
  16. A kinetic study of immune mediators in the lungs of mice infected with influenza A virus.
    J Immunol. 1992 Aug 1;149(3):932-9 PMID: 1321855
  17. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.
    J Exp Med. 1994 Apr 1;179(4):1273-83 PMID: 7908322
  18. Respiratory virus infection of mice provokes a permanent humoral immune response.
    J Virol. 1994 Sep;68(9):6083-6 PMID: 8057487
  19. Critical role of corneal Langerhans cells in the CD4- but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas.
    J Immunol. 1992 Apr 15;148(8):2522-9 PMID: 1313845
  20. Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells.
    J Immunol. 1992 Dec 1;149(11):3495-502 PMID: 1358972
  21. Interleukin-12 gene expression after viral infection in the mouse.
    J Virol. 1995 Mar;69(3):1955-8 PMID: 7853541
  22. Effects of IL-12 on the response and susceptibility to experimental viral infections.
    J Immunol. 1994 Feb 1;152(3):1253-64 PMID: 7905500
  23. Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist.
    Eur J Immunol. 1995 Jan;25(1):200-6 PMID: 7843232
  24. Immune interferon: a pleiotropic lymphokine with multiple effects.
    Immunol Today. 1985 Apr;6(4):131-6 PMID: 25289500
  25. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.
    J Exp Med. 1993 Apr 1;177(4):1199-204 PMID: 8096238
  26. Role of macrophage cytokines in influenza A virus infections.
    Immunobiology. 1993 Nov;189(3-4):340-55 PMID: 8125516
  27. Defense mechanisms against primary influenza virus infection in mice. I. The roles of interferon and neutralizing antibodies and thymus dependence of interferon and antibody production.
    J Immunol. 1977 Jan;118(1):256-63 PMID: 401512
  28. In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS).
    J Exp Med. 1994 Dec 1;180(6):2199-208 PMID: 7964495
  29. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers.
    J Exp Med. 1991 Apr 1;173(4):869-79 PMID: 1672545
  30. The interleukin-12 subunit p40 specifically inhibits effects of the interleukin-12 heterodimer.
    Eur J Immunol. 1993 Sep;23(9):2202-8 PMID: 8103745
  31. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells.
    J Immunol. 1991 May 1;146(9):3074-81 PMID: 1673147
  32. Human interferon alpha and gamma production by lymphocytes during the generation of influenza virus-specific cytotoxic T lymphocytes.
    J Gen Virol. 1986 Nov;67 ( Pt 11):2325-34 PMID: 3097247
  33. Characterization of early IL-12, IFN-alphabeta, and TNF effects on antiviral state and NK cell responses during murine cytomegalovirus infection.
    J Immunol. 1996 Jun 15;156(12):4746-56 PMID: 8648121
  34. Persistence of influenza virus-specific antibody-secreting cells and B-cell memory after primary murine influenza virus infection.
    Cell Immunol. 1987 Oct 1;109(1):53-64 PMID: 3498544
  35. Cloning and expression of murine IL-12.
    J Immunol. 1992 Jun 1;148(11):3433-40 PMID: 1350290
  36. Contribution of virus and immune factors to herpes simplex virus type I-induced corneal pathology.
    Invest Ophthalmol Vis Sci. 1990 Oct;31(10):1929-39 PMID: 2170289
  37. IL-12 stimulates an antiviral type 1 cytokine response but lacks adjuvant activity in IFN-gamma-receptor-deficient mice.
    J Immunol. 1995 Sep 1;155(5):2525-32 PMID: 7650382
  38. The in vivo antiviral activity of interleukin-12 is mediated by gamma interferon.
    J Virol. 1995 Dec;69(12):8147-50 PMID: 7494339
  39. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia.
    J Exp Med. 1993 Feb 1;177(2):475-82 PMID: 8426116
  40. IL-12 promotes enhanced recovery from vesicular stomatitis virus infection of the central nervous system.
    J Immunol. 1995 Dec 15;155(12):5684-9 PMID: 7499854
  41. Vesicular stomatitis virus infection of the central nervous system activates both innate and acquired immunity.
    J Virol. 1995 Oct;69(10):6466-72 PMID: 7545248
  42. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge.
    J Exp Med. 1992 Apr 1;175(4):1143-5 PMID: 1552285
  43. Roles of alpha beta and gamma delta T cell subsets in viral immunity.
    Annu Rev Immunol. 1992;10:123-51 PMID: 1534240
  44. Recovery from a viral respiratory infection. I. Influenza pneumonia in normal and T-deficient mice.
    J Immunol. 1981 Mar;126(3):1036-41 PMID: 6970211
  45. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo.
    Immunology. 1986 Jul;58(3):417-20 PMID: 2426185
  46. Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice.
    Eur J Immunol. 1995 Mar;25(3):672-6 PMID: 7705395
  47. Requirement for natural killer cell-produced interferon gamma in defense against murine cytomegalovirus infection and enhancement of this defense pathway by interleukin 12 administration.
    J Exp Med. 1995 Oct 1;182(4):1045-56 PMID: 7561678
  48. Influenza virus-specific antibody-secreting cells in the murine lung during primary influenza virus infection.
    J Virol. 1986 Nov;60(2):614-9 PMID: 3773053
  49. The immune response to influenza infection.
    Curr Top Microbiol Immunol. 1986;128:1-54 PMID: 3533447
  50. Tumor necrosis factor-alpha production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides.
    J Immunol. 1990 Sep 15;145(6):1921-8 PMID: 2391423
  51. Interleukin-12 treatment during immunization elicits a T helper cell type 1-like immune response in mice challenged with respiratory syncytial virus and improves vaccine immunogenicity.
    J Infect Dis. 1995 Sep;172(3):734-8 PMID: 7658066
  52. Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells.
    J Immunol. 1992 Jan 1;148(1):212-7 PMID: 1530795
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.6.4825-4831.1998
Published
1998-06-00
Pages
4825-31
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110027
Subset
IM
Grants
NCI NIH HHS · CA20833 · United States
NCI NIH HHS · R01 CA020833 · United States
NCI NIH HHS · P30 CA010815 · United States
NCI NIH HHS · CA10815 · United States
NIAID NIH HHS · AI34412 · United States
NIAID NIH HHS · R01 AI034412 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.6.4825-4831.1998 PMC Full Text View journal details
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