We have previously shown that mucosal immunization of BALB/c mice with Salmonella vector expressing cloned saliva-binding region (SBR) of Streptococcus mutans results in the induction of salivary and serum antibody responses to SBR. However, the role of host factors, including the Toll-like receptors (TLRs) has not been fully elucidated. Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and TLRs key molecules of the innate immune system trigger antimicrobial host defense responses. Objectives: To determine the role of TLRs in host responses to SBR expressed by a Salmonella vector. Methods: C57/BL6 wild type (wt), TLR2^-/-, TLR4^-/- and MyD88^-/- mice were immunized by the intranasal route with 1 x 10⁹ Salmonella containing the pGP1-2 and pSBR plasmids. Samples of serum and secretions were collected throughout the experiment and assessed for antibody activity by ELISA. Results: TLR2^-/-, TLR4^-/- and MyD88^-/- mice exhibit equivalent serum type 1 IgG and mucosal IgA antibody responses against SBR. Furthermore, TLR2^-/- mice exhibit a modestly reduced serum type 1 IgG response compared to the wt and TLR4^-/- mice following the booster immunization. Mucosal and systemic immune responses against SBR and Salmonella were lower in MyD88^-/- mice than others. Cytokine production by SBR specific CD₄⁺ T cells from TLR2^-/- mice was significantly elevated compared to that seen with wt mice. In contrast, pro-inflammatory cytokine production was not seen with SBR-stimulated CD₄⁺ T cells from MyD88^-/- mice. Conclusions: The results demonstrated that responses to Salmonella are mediated via TLR2 and TLR4, whereas responses to SBR are mediated via a TLR2 dependent pathway and MyD88 is essential to initiate both innate and adaptive immune responses against Salmonella and SBR of S. mutans. Supported by NIDCR grants DE 14215 and DE 09081.

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