Toll-like Receptor 2-and 4-Mediated Reciprocal Th17 and Antibody Responses to Group A Streptococcus Infection

Background: The role of Toll-like receptors (TLRs) in adaptive immunity is incompletely understood. Recurrent human infections by group A streptococcus (GAS) and associated autoimmune conditions suggest that the immunity to GAS is intricately regulated and that TLRs may be involved in the regulation. Methods: This study investigated adaptive mucosal immune responses to GAS in TLR2-/- and TLR4-/- mice with an intranasal infection model. Results: Flow cytometric analyses of nasal-associated lymphoid tissue (NALT) cells showed that robust T helper 17 (Th17) cell responses to GAS in wild-type (WT) mice were reduced in TLR2-/- mice by 50%. Conversely, antibody levels and follicular T and B cells in the germinal center of NALT were significantly higher in TLR2-/- than in WT mice. However, antibody response to soluble antigens coimmunized with GAS was similar in WT and TLR2-/- mice. Moreover, the adaptive clearance of GAS in TLR2-/- mice was as efficient as in WT mice, whereas it was significantly impaired in TLR4-/- mice in which antibody responses were significantly lower than in WT mice. Conclusions: Activation of TLR2 by GAS is responsible for massive Th17 activation and deficient antibody response, which may increase predisposition to GAS-related autoimmunity and reduce protection efficiency.