title: A modulatory interleukin-10 response to staphylococcal peptidoglycan prevents Th1/Th17 adaptive immunity to Staphylococcus aureus.
abstract: Toll-like receptor (TLR) 2 on antigen-presenting cells (APCs) enables these cells to recognize peptidoglycan-embedded lipopeptides and glycopolymers in the Staphylococcus aureus cell wall and mount an inflammatory response to this microbe. TLR2 signalling can also modulate immunity to S. aureus by inducing an interleukin (IL)-10 response in APCs. What determines the balance between proinflammatory and modulatory responses to S. aureus is unknown. We show that the modulatory IL-10 response preferentially occurs upon CD14- and CD36-independent TLR2 signaling, triggering PI3K activation, and is restricted to monocytes and monocyte-derived macrophages (MΦs). In contrast, monocyte-derived dendritic cells (DCs) produce mostly IL-12 and IL-23. The differential APC polarization induced by staphylococcal peptidoglycan translates into differential T helper responses: MΦs primarily trigger IL-10 and weak IL-17 responses, whereas DCs trigger a robust Th1/Th17 response. Exploitation of TLR2 signalling plasticity by S. aureus may explain the wide range of outcomes of human encounters with this microbe.
authors.affiliation: The Centre for Human Immunology, Departments of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Frodermann
authors.forename: Thu A
authors.initials: TA
authors.lastname: Chau
authors.forename: Samar
authors.initials: S
authors.lastname: Sayedyahossein
authors.forename: Judit M
authors.initials: JM
authors.lastname: Toth
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
authors.forename: Joaquín
authors.initials: J
authors.lastname: Madrenas
mesh_terms: D056704:Adaptive Immunity; D053492:Elafin / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D053492:Elafin; C508609:IL10 protein, human; C506806:PI3 protein, human; D010457:Peptidoglycan; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016753:Interleukin-10