Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis

Author:

Singh Tej Pratap12ORCID,Farias Amorim Camila1ORCID,Lovins Victoria M.2ORCID,Bradley Charles W.1ORCID,Carvalho Lucas P.34ORCID,Carvalho Edgar M.34ORCID,Grice Elizabeth A.2ORCID,Scott Phillip1ORCID

Affiliation:

1. School of Veterinary Medicine, University of Pennsylvania 1 Department of Pathobiology, , Philadelphia, PA, USA

2. Perelman School of Medicine, University of Pennsylvania 2 Department of Dermatology, , Philadelphia, PA, USA

3. Servico de Imunologia, Complexo Hospitalar Universitario Professor Edgard Santos, Universidade Federal da Bahia 3 , Salvador, Brazil

4. Laboratorio de Pesquisas Clinicas do Instituto de Pesquisas Goncalo Moniz, Fiocruz 4 , Salvador, Brazil

Abstract

Cutaneous leishmaniasis causes alterations in the skin microbiota, leading to pathologic immune responses and delayed healing. However, it is not known how these microbiota-driven immune responses are regulated. Here, we report that depletion of Foxp3+ regulatory T cells (Tregs) in Staphylococcus aureus–colonized mice resulted in less IL-17 and an IFN-γ–dependent skin inflammation with impaired S. aureus immunity. Similarly, reducing Tregs in S. aureus–colonized and Leishmania braziliensis–infected mice increased IFN-γ, S. aureus, and disease severity. Importantly, analysis of lesions from L. braziliensis patients revealed that low FOXP3 gene expression is associated with high IFNG expression, S. aureus burden, and delayed lesion resolution compared to patients with high FOXP3 expression. Thus, we found a critical role for Tregs in regulating the balance between IL-17 and IFN-γ in the skin, which influences both bacterial burden and disease. These results have clinical ramifications for cutaneous leishmaniasis and other skin diseases associated with a dysregulated microbiome when Tregs are limited or dysfunctional.

Funder

National Institutes of Health

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Reference82 articles.

1. Community differentiation of the cutaneous microbiota in psoriasis;Alekseyenko;Microbiome,2013

2. Regulatory T cells in skin facilitate epithelial stem cell differentiation;Ali;Cell,2017

3. Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis;Amorim;Sci. Transl. Med.,2019

4. Amorim, C.F., V.M.Lovins, T.P.Singh, F.O.Novais, J.C.Harris, A.S.Lago, L.P.Carvalho, D.P.Beiting, P.Scott, and E.A.Grice. 2023. The skin microbiome enhances disease through IL-1b and delays healing in cutaneous leishmaniasis patients.medRxiv. 10.1101/2023.02.02.23285247 (Preprint posted February 07, 2023).

5. CD4(+)CD25(−)Foxp3(−) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis;Anderson;J. Exp. Med.,2007

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3