Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Christopher von Beek, Grisna I. Prensa, Julia H. M. Andersson, Gunnar Pejler, Mikael E. Sellin
{"title":"Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria","authors":"Christopher von Beek,&nbsp;Grisna I. Prensa,&nbsp;Julia H. M. Andersson,&nbsp;Gunnar Pejler,&nbsp;Mikael E. Sellin","doi":"10.1002/eji.70040","DOIUrl":null,"url":null,"abstract":"<p>Mast cells (MCs) lodge within barrier tissues and respond to infectious microbes. Recent work demonstrated that MCs differentiate their cytokine response to extracellular versus invasive Gram-negative enterobacteria by a two-step activation mechanism that integrates Toll-like-receptor (TLR) sensing with signals elicited by type-III-secretion-system (TTSS) effectors during bacterial invasion. However, multiple MC subtypes exist, and it remains unclear how their phenotypic heterogeneity impacts microbial interactions. We find that murine MCs maintained in IL-3, or differentiated toward a connective-tissue phenotype (CT-MCs), respond potently to the enteropathogen <i>Salmonella enterica</i> Typhimurium (<i>S</i>.Tm) through two-step activation, with the TLR component explained by functional TLR4 and TLR2. By contrast, murine mucosal mast cells (M-MCs) express insignificant levels of these TLRs, therefore being unresponsive to extracellular <i>S</i>.Tm, but still mounting a response to invasive bacteria. Following invasion, MC granule maintenance by serglycin restricts <i>S</i>.Tm vacuolar and cytosolic colonization. Notably, this has no impact on the cytokine release from infected MCs, thus uncoupling <i>S</i>.Tm´s intracellular life-cycle from the MC cytokine response. Finally, human LUVA MCs employ a variant of two-step activation where TLR2/6 signaling combines with the TTSS-elicited signals. Together, this study explains how MC subtypes can respond differently to <i>S</i>.Tm-infection depending on their TLR expression and granule features.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70040","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.70040","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Mast cells (MCs) lodge within barrier tissues and respond to infectious microbes. Recent work demonstrated that MCs differentiate their cytokine response to extracellular versus invasive Gram-negative enterobacteria by a two-step activation mechanism that integrates Toll-like-receptor (TLR) sensing with signals elicited by type-III-secretion-system (TTSS) effectors during bacterial invasion. However, multiple MC subtypes exist, and it remains unclear how their phenotypic heterogeneity impacts microbial interactions. We find that murine MCs maintained in IL-3, or differentiated toward a connective-tissue phenotype (CT-MCs), respond potently to the enteropathogen Salmonella enterica Typhimurium (S.Tm) through two-step activation, with the TLR component explained by functional TLR4 and TLR2. By contrast, murine mucosal mast cells (M-MCs) express insignificant levels of these TLRs, therefore being unresponsive to extracellular S.Tm, but still mounting a response to invasive bacteria. Following invasion, MC granule maintenance by serglycin restricts S.Tm vacuolar and cytosolic colonization. Notably, this has no impact on the cytokine release from infected MCs, thus uncoupling S.Tm´s intracellular life-cycle from the MC cytokine response. Finally, human LUVA MCs employ a variant of two-step activation where TLR2/6 signaling combines with the TTSS-elicited signals. Together, this study explains how MC subtypes can respond differently to S.Tm-infection depending on their TLR expression and granule features.

Abstract Image

肥大细胞表型异质性影响致病性鼠伤寒沙门菌的相互作用
肥大细胞(MCs)驻扎在屏障组织内,对感染性微生物作出反应。最近的研究表明,MCs通过两步激活机制,将toll样受体(TLR)感知与iii型分泌系统(TTSS)效应物在细菌入侵过程中引发的信号结合起来,区分细胞因子对细胞外和侵袭性革兰氏阴性肠杆菌的反应。然而,存在多种MC亚型,其表型异质性如何影响微生物相互作用尚不清楚。我们发现维持IL-3或分化为结缔组织表型(CT-MCs)的小鼠MCs通过两步激活对肠致病菌沙门氏菌伤寒沙门氏菌(S.Tm)产生有效反应,其中TLR成分由功能性TLR4和TLR2解释。相比之下,小鼠粘膜肥大细胞(M-MCs)表达这些tlr的水平微不足道,因此对细胞外S.Tm无反应,但对侵入性细菌仍有反应。侵袭后,serglycin维持MC颗粒限制S.Tm液泡和细胞质定植。值得注意的是,这对受感染的MCs的细胞因子释放没有影响,从而将S.Tm的细胞内生命周期与MCs细胞因子反应分离开来。最后,人类LUVA MCs采用一种两步激活的变体,其中TLR2/6信号与ttss引发的信号结合。总之,这项研究解释了MC亚型如何根据其TLR表达和颗粒特征对s.tm感染做出不同的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信