The data strongly suggests that the mouse genetic background affects the type of IgG antibody response to pathogenic Leptospira; hyporesponsiveness to TLR4 may account for lower levels of IgG2a in the C3H-HeJ genetic background which result from impaired Th1 responses and could explain increased susceptibility to leptospirosis. This evidence concerns the gene TLR4 and leptospirosis.