TLR2 expression by B and myeloid cells contributes to the antibody response against Francisella tularensis lipoproteins

Abstract Bacterial lipoproteins are potent TLR2 agonists with significant immunogenic activity. However, it is unclear how TLR2 expression by B cells or other cell types can contribute to the humoral response against these Ags. Here, we demonstrate that the immunogenicity of Francisella tularensis lipoproteins Tul4 and FTT1103, in the absence of adjuvant, depends on their lipid moieties and, in part, on TLR2. Intraperitoneal immunization with Tul4 and FTT1103 elicits both T-dependent and T-independent Ab production, with TLR2 expression by B cells being critical for the T-independent production of IgM and IgG3. TLR2 expression by B cells and myeloid cells, but not T cells, played a major role in promoting T-dependent IgM and IgG production, except IgG1, whose induction was TLR2 independent. Mice immunized with Tul4 or FTT1103 were protected against tularemia, whereas immunization with the deacylated proteins was ineffective. Our study demonstrates, for the first time, to our knowledge, that B cell–intrinsic TLR2 expression is important for the humoral response against bacterial lipoproteins. These results may help in the design of more sophisticated vaccines against tularemia and other infections.