Activation-dependent modulation of Streptococcus pneumoniae-mediated death in human lymphocytes

Streptococcus pneumoniae (Spn) is a leading cause of community-acquired pneumonia, with infants and the elderly exhibiting significant susceptibility to the development of severe disease. A growing body of evidence supports the ability of Spn to negatively regulate the host response to infection, e.g. the capacity to induce death in numerous cell types. However, our understanding of the ability of Spn to directly impact lymphocytes remains limited. In this study, we tested the hypothesis that lymphocyte type and activation state influences the susceptibility to pneumococcus-mediated death. We show that in the resting state, CD4+ T cells exhibit a modestly increased susceptibility to Spn-induced death compared to CD8+ T cells or NK cells. In the presence of activating stimuli, the situation most reflective of what would occur in vivo during infection, all subsets demonstrated a significant increase in sensitivity to Spn-mediated death. Importantly, the activated subsets diverged dramatically in susceptibility with natural killer cells exhibiting an 8.6-fold greater sensitivity to pneumococcal components compared to the T-cell subsets. These results significantly expand our understanding of the capacity for pneumococcus to negatively regulate lymphocytes.