TLRs and Host Responses to Cloned SBR of Streptococcus mutans

We have previously shown that mucosal immunization of BALB/c mice with a Salmonella vector expressing the cloned saliva-binding region (SBR) of Streptococcus mutans results in the induction of a salivary and serum antibody response to SBR. However, the role of host factors, including the Toll-like receptors (TLRs) has not been fully elucidated. Objective: To investigate the role of MHC and TLRs in host responses to SBR and the Salmonella vector following mucosal immunization. Methods: BALB/c and C57/BL6 wild type (wt), TLR2^-/- and TLR4^-/- mice were immunized by the intranasal route on days 0 and 18 with 1 x 10⁹ Salmonella typhimurium BRD 509 containing the pGP1-2 and pSBR plasmids. Control mice received phosphate-buffered saline. Samples of serum and secretions were collected throughout the experiment and assessed for antibody activity by ELISA. Results: Significant anti-Salmonella and anti-SBR serum IgG antibody responses were observed in both BALB/c and C57BL/6 mice compared to controls (P < 0.0001). The levels of salivary IgA anti-Salmonella antibody activity induced in BALB/c and C57BL/6 mice were similar, whereas higher levels of salivary IgA anti-SBR antibody activity were observed in C57BL/6 than BALB/c mice. Serum IgG anti-Salmonella responses were lower in TLR2^-/- and TLR4^-/- mice compared to wt mice. However, serum IgG anti-SBR responses were lower in TLR2^-/- mice compared to that seen in wt and TLR4^-/- mice. A similar pattern was seen in terms of the salivary IgA anti-Salmonella and –SBR responses in these mice. Conclusion: Our results suggest a role of MHC in mucosal responses to SBR expressed by the Salmonella vector. Our results also indicate that responses to Salmonella are mediated via TLR2 and TLR4, whereas responses to the cloned SBR are mediated via a TLR2-dependent pathway. Supported by NIDCR grants DE 14215 and DE 09081.