The importance of TLR signaling in the induction of antibody production remains controversial. In one such study, it was shown that TLR is not required for mice to generate robust antibody response (Gavin et al., 2006) . Other researchers report that TLR signaling is critical for antibody production and isotype switching (Pasare and Medzhitov, 2005; Heer et al., 2007) . A recent study by Weiss et al. show that TLR2, TLR4, TLR2/TLR4, and MyD88 are not required for anti-Brucella IgG production (Weiss et al., 2005) . In contrast, our results reveal that production of Brucella specific IgG is delayed in TLR2 and TLR4 knockout mice and impaired in MyD88 knockout mice. Possible reasons for the discrepancies include the use of different Brucella species, B. melitensis 16 M vs B. abortus S19, differences in virulence and different routes of inoculation (aerosol exposure vs. intraperitoneal injection). Since IgM production is not affected by MyD88 deficiency and only transiently affected by TLR2 and TLR4 absence, we conclude that TLR2, TLR4 and MyD88 are critical for IgG class switch recombination, which might be critical to the control of Brucella infection, and should be considered when Brucella designing vaccines.