MyD88-Dependent Signaling Contributes to Protection following Bacillus anthracis Spore Challenge of Mice: Implications for Toll-Like Receptor Signaling

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.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady