title: Control of adaptive immune responses by Staphylococcus aureus through IL-10, PD-L1, and TLR2.
abstract: Microbes induce innate immune responses in hosts. It is critical to know how different microbes control adaptive responses through innate pathways. The impact of gram-positive bacteria on the innate and adaptive responses is unclear. Herein we report that Staphylococcus aureus induces IL-10, Th17-inducing cytokines IL-6 and IL-23, chemokines, and regulates dendritic cell markers. S. aureus inhibits T-cell IL-2 responses through modulation of HLA-DR, CD86 and PD-L1. IFN-gamma, Src kinase inhibitors, or TLR2 antibodies prevented the down-modulation of HLA-DR by S. aureus. Our data demonstrate that innate TLR signaling induces multi-dimensional inhibition of adaptive immune responses, which may contribute to the lack of protective immunity to bacteria or microbe tolerance. IL-10 and PD-L1 antagonists may boost immunity to vaccines for S. aureus and other microbes.
authors.affiliation: Laboratory of Immunology, Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research , Food and Drug Administration, Bethesda, MD 20892, USA. jinhai.wang@fda.hhs.gov
authors.forename: Jinhai
authors.initials: J
authors.lastname: Wang
authors.forename: Gregory
authors.initials: G
authors.lastname: Roderiquez
authors.forename: Michael A
authors.initials: MA
authors.lastname: Norcross
mesh_terms: D056704:Adaptive Immunity; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D019061:src-Family Kinases