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.
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Official URL: https://edoc.unibas.ch/75040/
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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 Ecology and Evolution Unit (Gagneux) |
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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: |
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edoc DOI: | |
Last Modified: | 05 Mar 2020 08:04 |
Deposited On: | 05 Mar 2020 08:04 |
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