IL-35 is critical in suppressing superantigenic Staphylococcus aureus -driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue

The human nasopharynx is frequently exposed to microbial pathogens, including superantigen-producing Staphylococcus aureus (SAg- Sau ), which activates potent pro-inflammatory T cell responses. However, cellular mechanisms that control SAg- Sau -driven T cell activation are poorly understood. Using human nasopharynx-associated lymphoid tissue (NALT), we show that SAg- Sau drove a strong Th17 activation, which was associated with an impaired CD4 + T cell-mediated immune regulation. This impairment of immune control correlated with a significant downregulation of interleukin-35 (IL-35) expression in tonsillar CD4 + T cells by SAg- Sau . Supplementing recombinant IL-35 suppressed SAg- Sau -activated Th17 responses, and this IL-35-mediated suppression positively correlated with the level of Th17 activation. Interestingly, SAg- Sau stimulation induced Foxp3 + Treg expansion and interleukin-10 (IL-10) production, which effectively suppressed the Th1 response, but failed to control the activation of Th17 cells. Overall, our results reveal an aberrant T cell regulation on SAg- Sau -driven Th17 activation and identify IL-35 as a critical cytokine to control superantigenic S.aureus -activated Th17 responses.