title: C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells.
abstract: Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB. DCIR is abundantly expressed in pulmonary lesions in Mycobacterium tuberculosis-infected nonhuman primates during both latent and active disease. In mice, we found that DCIR deficiency impairs STAT1-mediated type I IFN signaling in DCs, leading to increased production of IL-12 and increased differentiation of T lymphocytes toward Th1 during infection. As a consequence, DCIR-deficient mice control M. tuberculosis better than WT animals but also develop more inflammation characterized by an increased production of TNF and inducible NOS (iNOS) in the lungs. Altogether, our results reveal a pathway by which a C-type lectin modulates the equilibrium between infection-driven inflammation and pathogen's control through sustaining type I IFN signaling in DCs.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Troegeler
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mercier
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Cougoule
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Danilo
authors.initials: D
authors.lastname: Pietretti
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: André
authors.initials: A
authors.lastname: Colom
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Duval
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM U1104, CNRS UMR7280, Aix Marseille Université, F-13288 Marseille Cedex 09, France.
authors.forename: Thien-Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.affiliation: Service d'Histopathologie, INSERM/UPS-Unité de service 006/Centre Régional d'Exploration fonctionnelle et Ressources Expérimentales, Centre Hospitalier Universitaire Purpan, 31300 Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Capilla
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Poincloux
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Pingris
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Nigou
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rademann
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM U1104, CNRS UMR7280, Aix Marseille Université, F-13288 Marseille Cedex 09, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.affiliation: Department of Parasitology, Biomedical Primate Research Centre, 2288 GJ, Rijswijk, The Netherlands.
authors.forename: Frank A W
authors.initials: FA
authors.lastname: Verreck
authors.affiliation: Service d'Histopathologie, INSERM/UPS-Unité de service 006/Centre Régional d'Exploration fonctionnelle et Ressources Expérimentales, Centre Hospitalier Universitaire Purpan, 31300 Toulouse, France.
authors.forename: Talal
authors.initials: T
authors.lastname: Al Saati
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Geanncarlo
authors.initials: G
authors.lastname: Lugo-Villarino
authors.affiliation: Immunology Unit, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.|Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Lepenies
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Hudrisier
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, 31000 Toulouse, France; olivier.neyrolles@ipbs.fr.|IPBS, Université de Toulouse, Université Paul Sabatier (UPS), 31000 Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Neyrolles
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007370:Interferon Type I / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000276:immunology; D015398:Signal Transduction; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C526731:Dcir protein, mouse; D007370:Interferon Type I; D037181:Lectins, C-Type; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse
keywords: C-type lectin; inflammation; tuberculosis