MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling.
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-alpha) production in C3H/HeN, C3H/HeJ, and C57BL/6J bone marrow-derived macrophages. The ability of heat-killed B. anthracis to induce a TNF-alpha 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.
Hughes
Molly A
MA
Department of Internal Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, P.O. Box 800513, Charlottesville, VA 22908, USA. mah3x@virginia.edu
Green
Candace S
CS
Lowchyj
Lisa
L
Lee
Gloria M
GM
Grippe
Vanessa K
VK
Smith
Michael F
MF
Huang
Li-Yun
LY
Harvill
Eric T
ET
Merkel
Tod J
TJ
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000336:Aerosols; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001408:Bacillus anthracis / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013171:Spores, Bacterial / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000336:Aerosols; D000943:Antigens, Differentiation; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha