title: Anti-peptidoglycan antibodies and Fcγ receptors are the key mediators of inflammation in Gram-positive sepsis.
abstract: Gram-positive bacteria are an important public health problem, but it is unclear how they cause systemic inflammation in sepsis. Our previous work showed that peptidoglycan (PGN) induced proinflammatory cytokines in human cells by binding to an unknown extracellular receptor, followed by phagocytosis leading to the generation of NOD ligands. In this study, we used flow cytometry to identify host factors that supported PGN binding to immune cells. PGN binding required plasma, and plasma from all tested healthy donors contained IgG recognizing PGN. Plasma depleted of IgG or of anti-PGN Abs did not support PGN binding or PGN-triggered cytokine production. Adding back intact but not F(ab')₂ IgG restored binding and cytokine production. Transfection of HEK293 cells with FcγRIIA enabled PGN binding and phagocytosis. These data establish a key role for anti-PGN IgG and FcγRs in supporting inflammation to a major structural element of Gram-positive bacteria and suggest that anti-PGN IgG contributes to human pathology in Gram-positive sepsis.
authors: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors: Dawei
authors: D
authors: Sun
authors: Brent
authors: B
authors: Raisley
authors: Marybeth
authors: M
authors: Langer
authors: Janaki K
authors: JK
authors: Iyer
authors: Vidya
authors: V
authors: Vedham
authors: Jimmy L
authors: JL
authors: Ballard
authors: Judith A
authors: JA
authors: James
authors: Jordan
authors: J
authors: Metcalf
authors: K Mark
authors: KM
authors: Coggeshall
mesh_terms: D000907:Antibodies, Bacterial / Q000502:physiology*; D001408:Bacillus anthracis / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000502:physiology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D018836:Inflammation Mediators; D010457:Peptidoglycan; D017452:Receptors, IgG