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Background  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.    Methods  Memory 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.    Results  Th 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 .    Conclusions  As 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.

The Oral Commensal Streptococcus mitis Shows a Mixed Memory Th Cell Signature That Is Similar to and Cross-Reactive with Streptococcus pneumoniae