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

Abstract

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. This study investigated adaptive mucosal immune responses to GAS in TLR2-/- and TLR4-/- mice with an intranasal infection model. 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. 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.