MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: Implications for toll-like receptor signaling

Molly A. Hughes, Candace S. Green, Lisa Lowchyj, Gloria M. Lee, Vanessa K. Grippe, Michael F. Smith, Li Yun Huang, Eric T. Harvill, Tod J. Merkel

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41 Scopus citations

Abstract

Bacillus anthracis is a spore-forming, gram-positive organism that is the causative agent of the disease anthrax. Recognition of Bacillus anthracis by the host innate immune system likely plays a key protective role following infection. In the present study, we examined the role of TLR2, TLR4, and MyD88 in the response to B. anthracis. Heat-killed Bacillus anthracis stimulated TLR2, but not TLR4, signaling in HEK293 cells and stimulated tumor necrosis factor alpha (TNF-α) production in C3H/HeN, C3H/HeJ, and C57BL/6J bone marrow-derived macrophages. The ability of heat-killed B. anthracis to induce a TNF-α response was preserved in TLR2-/- but not in MyD88 -/- macrophages. In vivo studies revealed that TLR2-/- mice and TLR4-deficient mice were resistant to challenge with aerosolized Sterne strain spores but MyD88-/- mice were as susceptible as A/J mice. We conclude that, although recognition of B. anthracis occurs via TLR2, additional MyD88-dependent pathways contribute to the host innate immune response to anthrax infection.

Original languageEnglish (US)
Pages (from-to)7535-7540
Number of pages6
JournalInfection and Immunity
Volume73
Issue number11
DOIs
Publication statusPublished - Nov 1 2005

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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