Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

摘要: MyD88 −/− mice exhibit defective innate, diminished CD4 + T cell-dependent (TD) type 1, but enhanced 2, humoral immunity in response to intact Streptococcus pneumoniae (Pn). Because 1 IL-1R (IL-1R1) signaling is dependent, a role for endogenous IL-1 was determined. IL-1R1 , contrast exhibited relatively innate splenic cytokine expression Pn. Nevertheless, like were more sensitive killing with live Pn relative wild-type controls. Although elicited normal cell-independent IgM antipolysaccharide (PS) heat-killed Pn, the induction of PS- and protein-specific cognate, not noncognate, TD 2 IgG isotypes markedly reduced. Additionally, cells from Pn-primed failed elicit IFN-γ, IL-5, or IL-13 secretion upon restimulation vitro, whereas secreted levels IFN-γ IL-5 IL-13. In contrast, responses soluble, pneumococcal protein-PS conjugate, without adjuvant, showed little dependence on cell priming. These data are first demonstrate nonredundant immune an pathogen, although pathogen-derived soluble suggesting that antigenic context key determinant dependence. further suggest may be critical preserving Th2 function presence, absence, MyD88-dependent via TLRs.