Activation of memory Th17 cells by domain 4 pneumolysin in human nasopharynx-associated lymphoid tissue and its association with pneumococcal carriage

Abstract

Pneumococcal carriageiscommon in children thatmay account for the high incidenceofdisease in thisagegroup.Recent studies in animals suggest an important role for CD4 Tcells, T helper type 17 (Th17) cells in particular, in pneumococcal clearance. Whether this Th17-mediated mechanism operates in humans and what pneumococcal components activate Th17 are unknown.We investigated the ability of domain 4 pneumolysin (D4Ply) to activateCD4 Tcells including Th17 in human nasopharynx-associated lymphoid tissue (NALT) and peripheral blood.We show that D4Ply elicited a prominent CD4 T-cell proliferative response. More importantly, D4Ply elicited a significant memory Th17 response in NALT, and a moderate response inperipheral bloodmononuclear cells (PBMCs). ThisD4Ply-elicitedmemory Th17 responsewasmore marked in carriage than in carriage children in bothNALTand PBMCs. In contrast, no differencewas shown inD4Plyinduced Th1 response between the two groups. We also show D4Ply activated human monocytes and murine macrophages that was in part dependent on Toll-like receptor 4 (TLR-4). Our results support a protective role of Th17 against pneumococcal carriage in human nasopharynx, and identify a novel property of D4Ply to activate Th17 in NALT that may offer an attractive vaccine candidate in intranasal immunization against pneumococcal infection. © 2014 Society for Mucosal Immunology.