To determine the role of TLR signaling in antibody production and isotype switching, anti-Brucella IgM, IgG, IgG 1 , IgG 2a , and IgA responses were determined following aerosol infection. The results presented reveal detectable levels of IgM by 2 weeks p.i. that peaks by 4 weeks p.i. (Figure 5 , panel A). IgM levels begin to decline in the MyD88 −/− and C57BL/6 mice at 4 weeks p.i. while, IgM levels in the TLR2 −/− and TLR4 −/− mice plateau at 4 weeks with a gradual decline by 10 weeks p.i. Any requirement for TLR2 and TLR4 in IgM production is transient (only at 4 weeks p.i.). and IgM levels were never significantly different between MyD88 −/− and C57BL/6 mice throughout the experiment. Total Brucella-specific IgG in wild-type mice is detectable starting 4 weeks post-infection (Figure 5, panel B) , and increases continuously over the next 6 weeks. In contrast, elevation of the Brucella specific IgG levels is delayed in all of the knockout mice. Comparison among the groups revealed that, between weeks 4 and 8 p.i., IgG levels in TLR2 −/− and TLR4 −/− mice are significantly lower than that observed in the C57BL/6 mice. IgG levels increase in TLR4 −/− and TLR2 −/− mice by 10 weeks p.i. to levels that are not significantly different from the control C57BL/6 mice. In contrast, IgG levels in MyD88 −/− mice exhibit a significant reduction in titer over the course of infection. Serum IgA is not detected in the TLR2 −/− and TLR4 −/− mice, nor in C57BL/6 mice out to week 10 ( Figure 5 , panel C). Interestingly, serum IgA is prominent in the sera of MyD88 −/− mice and continuously increases over the course of the experiment.