Scientific Publications by FDA Staff

Infect Immun 2005 Nov;73(11):7535-40

MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling.

Hughes MA, Green CS, Lowchyj L, Lee GM, Grippe VK, Smith MF Jr, Huang LY, Harvill ET, Merkel TJ

Hughes MA, Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Infect Dis, POB 800513, Charlottesville, VA 22908 USA Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Infect Dis, Charlottesville, VA 22908 USA Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Gastroenterol, Charlottesville, VA 22908 USA US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Bethesda, MD USA US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD USA Penn State Univ, Dept Vet Sci, Immunol Res Labs, University Pk, PA 16802 USA

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.