The Host Peritoneal Cavity Harbors Prominent Memory Th2 and Early Recall Responses to an Intestinal Nematode.
The Host Peritoneal Cavity Harbors Prominent Memory Th2 and Early Recall Responses to an Intestinal Nematode.
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DOI：
10.3389/fimmu.2022.842870
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发表时间：
2022
影响因子：
7.3
通讯作者：
Hartmann S
中科院分区：
文献类型：
--
作者：
Yordanova IA;Jürchott K;Steinfelder S;Vogt K;Krüger U;Kühl AA;Sawitzki B;Hartmann S
肠道寄生线虫影响世界四分之一的人口，通常会引发显著的效应器Th2驱动的宿主免疫反应。由于并不是所有受感染的宿主都能保护自己免受再次感染，我们目前对线虫诱导的记忆Th2反应的理解仍然有限。在这里，我们研究了记忆Th2细胞的激活和驱动小鼠肠道线虫多回早期回忆反应的机制。我们发现，线虫治愈的小鼠在淋巴和非淋巴器官中具有不同转录水平的记忆Th2细胞，在肠系膜淋巴结(MLN)表达再循环标志CCR7和CD62-L，在肠道和腹膜(PEC)表达共刺激标志OX40，以及组织归巢和激活标志CCR2、CD69和CD40L。感染治愈后，记忆Th2细胞在淋巴组织和非淋巴组织中持续存在，尤其是腹膜记忆Th2细胞，在对挑战线虫感染的早期回忆反应中，最初表现出显著的扩张和强烈的寄生虫特异性Th2反应。这种效应与树突状细胞(DC)和嗜酸性粒细胞的大量涌入平行，这两种细胞也都只出现在再次感染的小鼠的腹膜腔中。此外，我们还发现，在腹膜间皮细胞(PEM)衬里的腹膜内，细胞黏附标记物VCAM-1和ICAM-1的基因表达水平在继发感染时显著降低。总体而言，我们的发现表明，宿主腹膜腔特别是拥有突出的记忆Th2细胞，似乎通过对细胞黏附标志物的不同调节，通过早期回忆反应直接对多脑回作出反应，这标志着腹膜腔是宿主对肠道病原体免疫反应的重要部位。
Intestinal parasitic nematodes affect a quarter of the world’s population, typically eliciting prominent effector Th2-driven host immune responses. As not all infected hosts develop protection against reinfection, our current understanding of nematode-induced memory Th2 responses remains limited. Here, we investigated the activation of memory Th2 cells and the mechanisms driving early recall responses to the enteric nematode Heligmosomoides polygyrus in mice. We show that nematode-cured mice harbor memory Th2 cells in lymphoid and non-lymphoid organs with distinct transcriptional profiles, expressing recirculation markers like CCR7 and CD62-L in the mesenteric lymph nodes (mLN), and costimulatory markers like Ox40, as well as tissue homing and activation markers like CCR2, CD69 and CD40L in the gut and peritoneal cavity (PEC). While memory Th2 cells persist systemically in both lymphoid and non-lymphoid tissues following cure of infection, peritoneal memory Th2 cells in particular displayed an initial prominent expansion and strong parasite-specific Th2 responses during early recall responses to a challenge nematode infection. This effect was paralleled by a significant influx of dendritic cells (DC) and eosinophils, both also appearing exclusively in the peritoneal cavity of reinfected mice. In addition, we show that within the peritoneal membrane lined by peritoneal mesothelial cells (PeM), the gene expression levels of cell adhesion markers VCAM-1 and ICAM-1 decrease significantly in response to a secondary infection. Overall, our findings indicate that the host peritoneal cavity in particular harbors prominent memory Th2 cells and appears to respond directly to H. polygyrus by an early recall response via differential regulation of cell adhesion markers, marking the peritoneal cavity an important site for host immune responses to an enteric pathogen.
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影响因子：
4.4
作者：
Jenkins, Stephen J.;Perona-Wright, Georgia;MacDonald, Andrew S.
通讯作者：
MacDonald, Andrew S.
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
DOI：
10.1073/pnas.2536517100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Lucas, S;Ghilardi, N;de Sauvage, FJ
通讯作者：
de Sauvage, FJ
影响因子：
4.4
作者：
Leitner, Judith;Grabmeier-Pfistershammer, Katharina;Steinberger, Peter
通讯作者：
Steinberger, Peter
影响因子：
16.6
作者：
Johnston CJC;Smyth DJ;Kodali RB;White MPJ;Harcus Y;Filbey KJ;Hewitson JP;Hinck CS;Ivens A;Kemter AM;Kildemoes AO;Le Bihan T;Soares DC;Anderton SM;Brenn T;Wigmore SJ;Woodcock HV;Chambers RC;Hinck AP;McSorley HJ;Maizels RM
通讯作者：
Maizels RM