C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells

Anthony Troegeler (1) , Ingrid Mercier (1) , Céline Cougoule (1) , Danilo Pietretti (1) , André Colom (2) , Carine Duval (3) , Thien-Phong Vu Manh (4) , Florence Capilla (5) , Renaud Poincloux (6) , Karine Pingris (1) , Jérôme Nigou (1) , Jörg Rademann (7) , Marc Dalod (4) , Frank a W Verreck (8) , Talal Al Saati (9) , Geanncarlo Lugo-Villarino (1) , Bernd Lepenies (10) , Denis Hudrisier (1) , Olivier Neyrolles (1)

1 IPBS - Institut de pharmacologie et de biologie structurale
2 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
3 Departament de Bioquímica i Biologia Molecular
4 CIML - Centre d'Immunologie de Marseille - Luminy
5 INSERM - Institut National de la Santé et de la Recherche Médicale
6 CDC - Compartimentation et dynamique cellulaires
7 Freie Universität Berlin
8 BPRC - Biomedical Primate Research Centre [Rijswijk]
9 Service Anatomie et cytologie pathologiques [CHU Toulouse]
10 Department of Biomolecular Systems [Potsdam]

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.

Domaines: Sciences du Vivant [q-bio]; Immunologie

Anthony Troegeler, Ingrid Mercier, Céline Cougoule, Danilo Pietretti, André Colom, et al.. C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (4), pp.E540-E549. ⟨10.1073/pnas.1613254114⟩. ⟨hal-02348507⟩