title: Staphylococcus aureusDownregulates IP-10 Production and Prevents Th1 Cell Recruitment.
abstract: Staphylococcal superantigens cause toxic shock syndrome, which is characterized by massive T cell activation and a predominant Th1 profile of cytokine production. However, superantigen-producingStaphylococcus aureusstrains are often part of the human nasal microbiome, and this carrier state has often been associated with some type 2 immune responses such as chronic sinusitis with polyps and atopic dermatitis. We have previously reported that theS. aureuscell wall downregulates the human T cell response to superantigens through a TLR2-dependent, IL-10-mediated mechanism. In this study, we show thatS. aureusalso regulates the profile of superantigen-induced T cell recruitment. The staphylococcal superantigen SEE induced the production of Th1 cell-recruiting chemokines, including IP-10, through an IFN-γ-dependent mechanism. Such an induction was suppressed by the concomitant presence ofS. aureusThe downregulation of IP-10 byS. aureuswas mediated by components of its cell wall, but was not due to peptidoglycan-induced IL-10 production. Instead,S. aureustriggered activation of MAPKs p38 and ERK, as well as inhibition of STAT1 signaling in monocytes, altogether contributing to the downregulation of IP-10 and other Th1 cell-recruiting chemokines (e.g., CXCL9 and CXCL11). These effects translated into inhibition of superantigen-induced Th1 cell recruitment. Taken together, our data may explain why colonization of superantigen-producingS. aureuscan induce, under some circumstances, mucosal type 2 immune responses.
authors.affiliation: Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada; and.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada; and.
authors.forename: Benoît
authors.initials: B
authors.lastname: Levast
authors.affiliation: Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada; and joaquin.madrenas@labiomed.org.|Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90277.
authors.forename: Joaquín
authors.identifier: 0000-0001-6191-3733
authors.initials: J
authors.lastname: Madrenas
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D054371:Chemokine CXCL11 / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D050794:STAT1 Transcription Factor / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D018089:Superantigens