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: Anthony Troegeler, Ingrid Mercier, Céline Cougoule, Danilo Pietretti, André Colom, Carine Duval, Thien-Phong Vu Manh, Florence Capilla, Renaud Poincloux, Karine Pingris, Jérôme Nigou, Jörg Rademann, Marc Dalod, Frank A W Verreck, Talal Al Saati, Geanncarlo Lugo-Villarino, Bernd Lepenies, Denis Hudrisier, Olivier Neyrolles
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 114 Issue 4 Pg. E540-E549 (01 24 2017) ISSN: 1091-6490 [Electronic] United States
• PMID: 28069953 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dcir protein, mouse
• Interferon Type I
• Lectins, C-Type
• STAT1 Transcription Factor
• Stat1 protein, mouse

Topics

• Animals
• Dendritic Cells (immunology)
• Female
• Interferon Type I (immunology)
• Lectins, C-Type (genetics, immunology)
• Macaca mulatta
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphorylation
• STAT1 Transcription Factor (immunology)
• Signal Transduction
• Tuberculosis (immunology)