Abstract

Abstract Our previous studies using intact Streptococcus pneumoniae type 14 (Pn14) (Gram-positive) and Neisseria meningitidis (Gram-negative) indicated distinct differences in the regulation of the associated polysaccharide (PS)-specific IgG responses. In light of potentially unique contributions of biochemically distinct capsular PS and their characteristic attachments to the underlying bacterium, it remains unresolved whether different bacterial sub-capsular domains can exert differential effects on PS-specific Ig responses. In this study, we utilized a mutant strain of group B Streptococcus (S. agalactiae) type III (GBS-III) that expresses desialylated IIIPS, biochemically identical to type 14 capsular PS (PPS14) of Pn14, to directly compare the PPS14-specific IgG responses to two distinct Gram-positive bacteria. Although both GBS-III and Pn14 elicited relatively rapid primary IgG anti-PPS14 responses that were dependent on CD4+ T cells, CD40L and CD28 costimulation, only GBS-III induced a highly boosted ICOS-dependent PPS14 specific IgG response. Of note, priming with Pn14 and boosting with GBS-III, although not isolated PPS14, elicited a similarly boosted PPS14-specific IgG response that was T cell- dependent. This indicates that Pn14 primes for memory but, unlike GBS-III, fails to elicit it. These data establish that structurally identical capsular PS expressed by two distinct Gram-positive extracellular bacteria can indeed elicit distinct PS specific IgG responses.

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