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CR3 Engaged by PGL-I Triggers Syk-Calcineurin-NFATc to Rewire the Innate Immune Response in Leprosy
- Source :
- Frontiers in Immunology, Vol 10 (2019)
- Publication Year :
- 2019
- Publisher :
- Frontiers Media S.A., 2019.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 10
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8552c01dc9144b9891319eb8b8538c48
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fimmu.2019.02913