Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response
Mouna Rahabi, Godefroy Jacquemin, Mélissa Prat, Etienne Meunier, Mohamad AlaEddine, Bénédicte Bertrand, Lise Lefèvre, Khaddouj Benmoussa, Philippe Batigne, Agnès Aubouy, Johan Auwerx, Sylvain Kirzin, Delphine Bonnet, Marie Danjoux, Bernard Pipy, Laurent Alric, Hélène Authier, Agnès Coste, Mouna Rahabi, Godefroy Jacquemin, Mélissa Prat, Etienne Meunier, Mohamad AlaEddine, Bénédicte Bertrand, Lise Lefèvre, Khaddouj Benmoussa, Philippe Batigne, Agnès Aubouy, Johan Auwerx, Sylvain Kirzin, Delphine Bonnet, Marie Danjoux, Bernard Pipy, Laurent Alric, Hélène Authier, Agnès Coste
Abstract
Colonic macrophages are considered to be major effectors of inflammatory bowel diseases (IBDs) and the control of gut inflammation through C-type lectin receptors is an emerging concept. We show that during colitis, the loss of dectin-1 on myeloid cells prevents intestinal inflammation, while the lack of mannose receptor (MR) exacerbates it. A marked increase in dectin-1 expression in dextran sulfate sodium (DSS)-exposed MR-deficient mice supports the critical contribution of dectin-1 to colitis outcome. Dectin-1 is crucial for Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon as precursors of inflammatory macrophages. Dectin-1 also promotes inflammasome-dependent interleukin-1β (IL-1β) secretion through leukotriene B4 production. Interestingly, colonic inflammation is associated with a concomitant overexpression of dectin-1/CCL2/LTA4H and downregulation of MR on macrophages from IBD patients. Thus, MR and dectin-1 on macrophages are important mucosal inflammatory regulators that contribute to the intestinal inflammation.
Trial registration: ClinicalTrials.gov NCT01990716.
Keywords: C-type lectin receptor; Dectin-1; IBD; colitis; inflammatory bowel disease; innate immune response; macrophage; mannose receptor; mucosal immmunity.
Conflict of interest statement
Declaration of Interests The authors declare no competing interests.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed