Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Toll-like receptor 2-and 4-mediated reciprocal Th17 and antibody responses to group A streptococcus infection (#58)

Beinan Wang 1
  1. Institute of Microbiology, Chinese Academy of Science, Beijing , China

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 TLRs may be involved in the regulation.

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

Results: FACS analyses of Nasal-Associated Lymphoid Tissue (NALT) cells showed that robust Th17 responses to GAS in WT mice were reduced in TLR2-/- mice by 50%. Conversely, antibody levels and follicular T (Tfh) and B cells in germinal center of NALT were significantly higher in TLR2-/-than in WT mice. However, antibody response to soluble antigens co-immunized 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.

Conclusion: 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 efficiency of protection.

Key words: Group A Streptococcus (GAS); Toll-like receptor 2 (TLR2); Toll-like receptor 4 (TLR4); Th17; Mucosal immunity.