IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue |
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| Institution: | 1. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK;2. ENT Department, Alder Hey Children''s Hospital, Liverpool, UK;3. ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK;4. Institute of Tissue Engineering and Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK;1. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK;2. ENT Department, Alder Hey Children''s Hospital, Liverpool, UK;3. ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK;4. Institute of Tissue Engineering and Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK |
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| Abstract: | 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. |
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