title: Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function.
abstract: ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice. This was associated with substantially reduced uptake, phagocytosis, and intracellular killing of both Gram-positive and Gram-negative bacteria by ST2-deficient phagocytes. Consistent with a reduced antimicrobial response, phagocytes lacking ST2 displayed a defect in bactericidal activity in response to bacterial challenges with severely impaired phagosome maturation and NOX2 function. Thus, ST2-deficient mice exhibit an increased susceptibility to polymicrobial infection with impaired bacterial clearance, which is associated with defects in phagosome maturation and NOX2-derived production of reactive oxygen species characterized in ST2-deficient phagocytes.
authors.affiliation: Department of Academic Surgery, University College Cork/National University of Ireland, Cork University Hospital, Cork, Ireland.
authors.forename: Julliette M
authors.initials: JM
authors.lastname: Buckley
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Liu
authors.forename: Chong Hui
authors.initials: CH
authors.lastname: Li
authors.forename: Siobhan
authors.initials: S
authors.lastname: Blankson
authors.forename: Qiong Di
authors.initials: QD
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: H Paul
authors.initials: HP
authors.lastname: Redmond
authors.forename: Jiang Huai
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000276:immunology* / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology* / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D018123:Receptors, Interleukin; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases