CR3 engaged by PGL-I triggers Syk-calcineurin-NFATc to rewire the innate immune response in Leprosy
| Autor: | Doz-Deblauwe, Emilie, Carreras, Florence, Arbues, Ainhoa, Remot, Aude, Epardaud, Mathieu, Malaga, Wladimir, Mayau, Véronique, Prandi, Jacques, Astarie-Dequeker, Catherine, Guilhot, Christophe, Demangel, Caroline |
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| Přispěvatelé: | Winter, Nathalie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
CR3
Mycobacterium leprae NFAT Syk dendritic cell macrophage neutrophil phenol glycolipid-1 Immunologie Immunology Microbiology and Parasitology cytokine chemical and pharmacologic phenomena hemic and immune systems mycobacterium leprae réponse immunitaire innée modèle murin Microbiologie et Parasitologie |
| Zdroj: | Frontiers in Immunology (10), 15 p.. (2019) |
| Popis: | Mycobacterium leprae, the causative agent of leprosy, is unique amongst human pathogens in its capacity to produce the virulence factor phenolic glycolipid (PGL)-I. In addition to mediating bacterial tropism for neurons, PGL-I interacts with Complement Receptor (CR)3 on macrophages (MPs) to promote infection. We demonstrate here that PGL-I binding to CR3 also enhances bacterial invasion of both polymorphonuclear neutrophils (PMNs) and dendritic cells (DCs). Moreover, in all cell types CR3 engagement by PGL-I activates the Syk tyrosine kinase, inducing calcineurin-dependent nuclear translocation of the transcription factor NFATc. This selectively augments the production of IL-2 by DCs, IL-10 by PMNs and IL-1β by MPs. In intranasally-infected mice PGL-I binding to CR3 heightens mycobacterial phagocytosis by lung PMNs and MPs, and stimulates NFATc-controlled production of Syk-dependent cytokines. Our study thus identifies the CR3-Syk-NFATc axis as a novel signaling pathway activated by PGL-I in innate immune cells, rewiring host cytokine responses to M. leprae. |
| Databáze: | OpenAIRE |
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