Erythema Nodosum Leprosum Neutrophil Subset Expressing IL-10R1 Transmigrates into Skin Lesions and Responds to IL-10.

Abstract

Erythema nodosum leprosum (ENL) is an inflammatory complication in leprosy. Yet, the involvement of ENL neutrophils in the inflammatory response against Mycobacterium leprae remains poorly explored. Our primary aim was to investigate the utility of the surface expression of neutrophil IL-10R1 as an ENL biomarker and, secondarily, to evaluate whether leprosy or healthy M. leprae-stimulated neutrophils produce cytokines and are able to respond to IL-10. We, in this study, describe a subpopulation of circulating neutrophils of ENL patients that exclusively expressed IL-10R1, providing evidence that IL-10R1+ neutrophils are present in ENL lesions. It was also found that ENL neutrophils, but not those of nonreactional leprosy controls, were able to secret detectable levels of TNF ex vivo and the addition of IL-10 blocked TNF release. It was likewise observed that M. leprae-stimulated, healthy neutrophils expressed IL-10R1 in vitro, and ENL-linked cytokines were released by M. leprae-cultured neutrophils in vitro. Moreover, consistent with the presence of a fully functional IL-10R, the addition of IL-10 prevented the release of M. leprae-induced cytokines. Most importantly, dead M. leprae revealed its superior capacity to induce CCL4 and IL-8 in primary neutrophils over live Mycobacterium, suggesting that M. leprae may hamper the inflammatory machinery as an immune escape mechanism.

• Authors: Fabiana Santos Pacheco, Rhana Berto da Silva Prata, Sheila Santos Brandão, Helen Ferreira, Thaís Fernanda Rodrigues, Jéssica Brandão Dos Santos, Camila Oliveira da Silva, Isabella Forasteiro Tavares, Mayara Abud Mendes, Ana Carolina Duarte Pereira Rodrigues, Alice de Miranda Machado, José Augusto da Costa Nery, Thaís Porto Amadeu, Milton Ozório Moraes, Euzenir Nunes Sarno, Veronica Schmitz
• Journal: ImmunoHorizons (Immunohorizons) Vol. 4 Issue 2 Pg. 47-56 (02 07 2020) ISSN: 2573-7732 [Electronic] United States
• PMID: 32034084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors.

Chemical References

• Cytokines
• Inflammation Mediators
• Interleukin-10 Receptor alpha Subunit
• Interleukin-10
• Thalidomide

Topics

• Adult
• Cells, Cultured
• Cytokines (metabolism)
• Erythema Nodosum (drug therapy, immunology)
• Female
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-10 (pharmacology)
• Interleukin-10 Receptor alpha Subunit (metabolism)
• Leprosy, Lepromatous (drug therapy, immunology)
• Male
• Middle Aged
• Mycobacterium leprae (immunology)
• Neutrophil Infiltration (drug effects)
• Neutrophils (drug effects, metabolism, microbiology)
• Skin (immunology)
• Thalidomide (therapeutic use)
• Young Adult