The lipid attachment in OspA seems to be a critical determinant of the mature protein immunogenicity [35] . Furthermore, the OspA leader peptide has been fused to different proteins to generate potent lipo-antigens that induce strong B (IgG) and T-cell (helper CD4 + and cytotoxic CD8+) responses [44] , [45] . Because lipoproteins and OspA are known to trigger TLR2-based receptors [46] , [47] , we stimulated monocyte derived dendritic cells with purified proteins in order to access the effect of the naked protein on cytokine induction. We observed that wildtype OspA ( wt OspA) induced TNFa and IL-10 but it did not induce IL-12 or IFNc. In the absence of the leader peptide, as in mut OspA, the TNFa response was abrogated and IL-10 was reduced in half. In contrast, if OspA is delivered in Lactobacillus we also observe an effect on the production of IL-12. This effect appears to be related to the delivery vehicle in which OspA is presented. Furthermore, our results show that mutation of the Cys 17 on the leader peptide of OspA decreases significantly the production of pro-and antiinflammatory cytokines, and that this effect is related to the lipidation of OspA. In addition, we observed that lipidation of protein is not essential to induce a specific humoral immune response to OspA (systemic IgG and mucosal IgA) when the antigen is orally delivered by Lactobacillus. The adjuvant effect of Lactobacillus as oral carrier, exerts a synergized effect along with the intrinsic antigenicity of unlipidated OspA. This result differs with others, where the lipid modification of OspA seems to be essential to induce a humoral immune response, when the soluble unlipidated antigen is delivered subcutaneously without a cellular carrier [35] . In addition, we have found that the mutation of OspA Cys 17 skewed the systemic IgG production towards IgG2a, probably as result of a shift from a Th2 to a Th1 response. Over all, our data suggest that the lipidation of OspA has a clear role on the mixed Th1/Th2 cellular and humoral immune response to orally administered Lactobacillus expressing OspA.