Abstract
BackgroundCarriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized.MethodsMemory CD4+ T helper (Th) cell subsets were isolated from healthy human blood donors according to differential expression of chemokine receptors, expanded in vitro using polyclonal stimuli and characterized for reactivity against different streptococcal strains.ResultsTh cells responding to S. mitis, S. salivarius and S. pneumoniae were predominantly in a CCR6+CXCR3+ subset and produced IFN-γ, and in a CCR6+CCR4+ subset and produced IL-17 and IL-22. Frequencies of S. pneumoniae-reactive Th cells were higher than frequencies of S. mitis- and S. salivarius-specific Th cells. S. mitis and S. pneumoniae isogenic capsule knock-out mutants and a S. mitis mutant expressing the serotype 4 capsule of S. pneumoniae showed no different Th cell responses as compared to wild type strains. S. mitis-specific Th17 cells showed cross-reactivity with S. pneumoniae.ConclusionsAs Th17 cells partly control clearance of S. pneumoniae, cross-reactive Th17 cells that may be induced by commensal bacterial species may influence the immune response, independent of capsule expression.
Highlights
A reciprocal beneficial relationship has developed between hosts and their symbionts throughout evolution
Utilizing a T cell screening method, we found that memory T helper (Th) cells reactive against S. mitis and S. salivarius are predominantly found in the CCR6+ Th1 and T helper 17 (Th17) subsets, a distribution similar to that obtained for S. pneumoniae
Circulating T helper memory cells show a heterogeneous signature after stimulation with S. mitis, similar to that obtained with S. pneumoniae
Summary
A reciprocal beneficial relationship has developed between hosts and their symbionts throughout evolution. In the human oral cavity, more than 700 bacterial species can be found [1,2] of which a healthy person can host more than 200 [3]. In order for the commensals to persist in their niches, it is important that adequate host-microbe interplay is established. This comprises immune exclusion by keeping microbes from interacting with host cell by mucus, SIgA and/or antimicrobial peptides, and immune elimination by innate and adaptive responses without the induction of inflammation [4]. S. mitis is a pioneer bacterial species that colonizes the nasopharynx and all sites of the oral cavity from early infancy. Carriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized
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