edoc

CR3 engaged by PGL-I triggers syk-calcineurin-NFATc to rewire the innate immune response in leprosy

Doz-Deblauwe, Émilie and Carreras, Florence and Arbues, Ainhoa and Remot, Aude and Epardaud, Mathieu and Malaga, Wladimir and Mayau, Véronique and Prandi, Jacques and Astarie-Dequeker, Catherine and Guilhot, Christophe and Demangel, Caroline and Winter, Nathalie. (2019) CR3 engaged by PGL-I triggers syk-calcineurin-NFATc to rewire the innate immune response in leprosy. Frontiers in Immunology, 10. p. 2913.

[img] PDF - Published Version
Available under License CC BY (Attribution).

1633Kb

Official URL: https://edoc.unibas.ch/75040/

Downloads: Statistics Overview

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; .
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Arbues Arribas, Ainhoa
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Frontiers Media
e-ISSN:1664-3224
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:05 Mar 2020 08:04
Deposited On:05 Mar 2020 08:04

Repository Staff Only: item control page