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PMID: 16622218 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Toll-like receptor 2 is required for inflammatory responses to Francisella tularensis LVS.

Infection and immunity ·Vol. 74 ·No. 5 ·2006-05-00 ·Pages 2809-16

Katz J, Zhang P, Martin M, Vogel SN, Michalek SM

Abstract

Francisella tularensis, a gram-negative bacterium, is the etiologic agent of tularemia and has recently been classified as a category A bioterrorism agent. Infections with F. tularensis result in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms mediating this response have not been completely elucidated. In the present study, we determined the role of Toll-like receptors (TLRs) in mediating inflammatory responses to F. tularensis LVS, and the role of NF-kappaB in regulating these responses. Stimulation of bone marrow-derived dendritic cells from C57BL/6 wild-type (wt) and TLR4-/- but not TLR2-/- mice, with live F. tularensis LVS elicited a dose-dependent increase in the production of tumor necrosis factor alpha. F. tularensis LVS also induced in a dose-dependent manner an up-regulation in the expression of the costimulatory molecules CD80 and CD86 and of CD40 and the major histocompatibility complex class II molecules on dendritic cells from wt and TLR4-/- but not TLR2-/- mice. TLR6, not TLR1, was shown to be involved in mediating the inflammatory response to F. tularensis LVS, indicating that the functional heterodimer is TLR2/TLR6. Stimulation of dendritic cells with F. tularensis resulted in the activation of NF-kappaB, which resulted in a differential effect on the production of pro- and anti-inflammatory cytokines. Taken together, our results demonstrate the role of TLR2/TLR6 in the host's inflammatory response to F. tularensis LVS in vitro and the regulatory function of NF-kappaB in modulating the inflammatory response.

MeSH Terms
Animals B7-1 Antigen/analysis B7-2 Antigen/analysis CD40 Antigens/analysis Francisella tularensis/immunology Inflammation/etiology Interleukin-10/biosynthesis Mice Mice, Inbred C57BL NF-kappa B/physiology Toll-Like Receptor 1/physiology Toll-Like Receptor 2/physiology Toll-Like Receptor 4/physiology Toll-Like Receptor 6/physiology Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
B7-1 Antigen B7-2 Antigen CD40 Antigens Cd86 protein, mouse NF-kappa B Tlr2 protein, mouse Tlr4 protein, mouse Tlr6 protein, mouse Toll-Like Receptor 1 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptor 6 Tumor Necrosis Factor-alpha Interleukin-10
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Katz Jannet
Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zhang Ping
Martin Michael
Vogel Stefanie N
Michalek Suzanne M
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.74.5.2809-2816.2006
Published
2006-05-00
Pages
2809-16
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1459727
Subset
IM
Grants
NIAID NIH HHS · AI57168 · United States
NIDCR NIH HHS · R01 DE014215 · United States
NIDCR NIH HHS · R56 DE014215 · United States
NIDCR NIH HHS · DE14215 · United States
NIDCR NIH HHS · DE09081 · United States
NIAID NIH HHS · U54 AI057168 · United States
NIAID NIH HHS · AI56460 · United States
NIDCR NIH HHS · R01 DE009081 · United States
NIAID NIH HHS · U01 AI056460 · United States
External Links
PubMed source DOI: 10.1128/IAI.74.5.2809-2816.2006 PMC Full Text View journal details
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