CR3 Engaged by PGL-I Triggers Syk-Calcineurin-NFATc to Rewire the Innate Immune Response in Leprosy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Jan 11

PMID 31921172

Citations 14

Authors

Emilie Doz-Deblauwe

Florence Carreras

Ainhoa Arbues

Aude Remot

Mathieu Epardaud

Wladimir Malaga

Veronique Mayau

Jacques Prandi

Catherine Astarie-Dequeker

Christophe Guilhot

Caroline Demangel

Nathalie Winter

Affiliations

Soon will be listed here.

Abstract

, 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 .

Citing Articles

Leprosy.

Grijsen M, Nguyen T, Pinheiro R, Singh P, Lambert S, Walker S Nat Rev Dis Primers. 2024; 10(1):90.

PMID: 39609422 DOI: 10.1038/s41572-024-00575-1.

An update on leprosy immunopathogenesis: systematic review.

Silva M, Silva C, Brasil T, Alves A, Dos Santos E, Frota C Front Immunol. 2024; 15:1416177.

PMID: 39308868 PMC: 11412872. DOI: 10.3389/fimmu.2024.1416177.

Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1.

Doz-Deblauwe E, Bounab B, Carreras F, Fahel J, Oliveira S, Lamkanfi M Life Sci Alliance. 2024; 7(7.

PMID: 38803236 PMC: 11109925. DOI: 10.26508/lsa.202402623.

Immunopathogenesis of Type 1 and Type 2 Leprosy Reaction: An Update Review.

Dewi D, Djatmiko C, Rachmawati I, Arkania N, Wiliantari N, Nadhira F Cureus. 2023; 15(11):e49155.

PMID: 38130570 PMC: 10733783. DOI: 10.7759/cureus.49155.

The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia.

Langouet-Astrie C, Oshima K, McMurtry S, Yang Y, Kwiecinski J, LaRiviere W Cell Rep. 2022; 41(9):111721.

PMID: 36450248 PMC: 10082619. DOI: 10.1016/j.celrep.2022.111721.

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