1. CD89 Is a Potent Innate Receptor for Bacteria and Mediates Host Protection from Sepsis.
- Author
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de Tymowski C, Heming N, Correia MDT, Abbad L, Chavarot N, Le Stang MB, Flament H, Bex J, Boedec E, Bounaix C, Soler-Torronteras R, Denamur E, Galicier L, Oksenhendler E, Fehling HJ, Pinheiro da Silva F, Benhamou M, Monteiro RC, and Ben Mkaddem S
- Subjects
- Animals, Antigens, CD genetics, C-Reactive Protein metabolism, Cytokines metabolism, Dendritic Cells cytology, Dendritic Cells immunology, Dendritic Cells metabolism, Disease Models, Animal, Female, Humans, Immunocompromised Host, Immunoglobulin A blood, Immunoglobulin A immunology, Immunoglobulin A metabolism, Kaplan-Meier Estimate, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocytes cytology, Monocytes immunology, Monocytes metabolism, Phagocytosis, Pneumonia mortality, Pneumonia pathology, Receptors, Fc genetics, Sepsis immunology, Antigens, CD metabolism, Escherichia coli physiology, Receptors, Fc metabolism, Sepsis prevention & control, Streptococcus pneumoniae physiology
- Abstract
Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein (CRP). This binding is only partially inhibited by serum IgA and induces bacterial phagocytosis by CD11c
+ dendritic cells and monocytes and/or macrophages, suggesting a physiological role in innate host defense. Blood phagocytes from common variable immunodeficiency patients bind, internalize, and kill bacteria in a CD89-dependent manner, confirming the IgA independence of this mechanism. In vivo, CD89 transgenic mice are protected in two different models of sepsis: a model of pneumonia and the cecal ligation and puncture (CLP) polymicrobial model of infection. These data identify CD89 as a first-line innate receptor for bacterial clearance before adaptive responses can be mounted. Fc receptors may emerge as a class of innate receptors for various bacteria with pleiotropic roles., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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