The contribution of humoral immunity to the outcome of Brucella infection is controversial. IgM may enhance opsonic uptake or the activity of complement. However, the differences in IgM production between knockouts are only transitory and have no correlation with differences in immune clearance. In general, IgG levels are significantly reduced in each of the knockout mice. However, the effect in the TLR4 and TLR2 knockouts is transient, while reduced IgG levels are consistently observed in the absence of MyD88 function. A second marker associated with the loss of MyD88 is the significant level of circulating IgA observed in the MyD88 knockout mice. Surprisingly, serum IgA levels were elevated in MyD88 −/− mice, but not in TLR2 −/− and TLR4 −/− mice following Brucella infection, suggesting that the IgA class switch recombination or secretion is enhanced in MyD88 knockout mice. Alternatively, higher Brucella burden in the lung constantly stimulates IgA secretion. However, this hypothesis is not supported by the fact that serum IgA is not detected in the TLR2 and TLR4 knockout mice despite similar levels of bacterial burden in the lung. In fact, this phenomenon has been previously reported in MyD88 −/− mice orally vaccinated with attenuated Salmonella expressing a Streptococcus pneumoniae surface antigen (Park et al., 2008) . It could prove useful to understand the biological mechanism involved and its potential application to vaccine design. The contribution of either elevated IgA or suppressed IgG to the inability of MyD88 knockouts to control infection is under investigation.