Bibliographic Details
| Title: |
CR3 Engaged by PGL-I Triggers Syk-Calcineurin-NFATc to Rewire the Innate Immune Response in Leprosy |
| Authors: |
Émilie Doz-Deblauwe, Florence Carreras, Ainhoa Arbues, Aude Remot, Mathieu Epardaud, Wladimir Malaga, Véronique Mayau, Jacques Prandi, Catherine Astarie-Dequeker, Christophe Guilhot, Caroline Demangel, Nathalie Winter |
| Source: |
Frontiers in Immunology, Vol 10 (2019) |
| Publisher Information: |
Frontiers Media S.A., 2019. |
| Publication Year: |
2019 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
NFAT, Syk, CR3, phenol glycolipid-1, Mycobacterium leprae, dendritic cell, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02913/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2019.02913 |
| Access URL: |
https://doaj.org/article/8552c01dc9144b9891319eb8b8538c48 |
| Accession Number: |
edsdoj.8552c01dc9144b9891319eb8b8538c48 |
| Database: |
Directory of Open Access Journals |
