CX3CR1-Expressing Myeloid Cells Regulate Host-Helminth Interaction and Lung Inflammation.
CX3CR1-Expressing Myeloid Cells Regulate Host-Helminth Interaction and Lung Inflammation.
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DOI：
10.1002/adbi.202101078
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发表时间：
2022-03
期刊：
影响因子：
3.7
通讯作者：
Nair MG
中科院分区：
文献类型：
--
作者：
Kim SY;Barnes MA;Sureshchandra S;Menicucci AR;Patel JJ;Messaoudi I;Nair MG
许多蠕虫的生命周期，包括钩虫，涉及一个强制性的肺阶段，其中髓细胞和粒细胞亚群与蠕虫相互作用，并对感染引起的肺损伤作出反应。为了评估这些先天性亚群，我们采用巴西日本圆线虫感染的报告小鼠骨髓细胞（CX 3CR 1GFP）和粒细胞（PGRPdsRED）。日本圆线虫感染诱导报告细胞的肺浸润，包括CX 3CR 1+髓样细胞和PGRP+嗜酸性粒细胞。引人注目的是，与CX 3CR 1 +/+小鼠相比，CX 3CR 1缺陷的CX 3CR 1GFP/GFP小鼠免受日本圆线虫感染，体重减轻，肺白细胞浸润和蠕虫负荷减少。这种保护作用对CX 3CR 1是特异性的，因为CCR 2缺陷小鼠没有表现出减少的蠕虫负担。与肺Ly 6C+单核细胞或CD 11 c+细胞共培养的日本圆线虫表明，CX 3CR 1GFP/GFP单核细胞分泌更多的促炎细胞因子，并主动结合寄生虫，导致运动性降低。Ly 6C+或CD 11 c+细胞的RNA测序显示了日本圆线虫诱导的基因表达变化，特别是在单核细胞中，与炎症，趋化性和细胞外基质重塑途径相关。我们还确定了细胞毒性和粘附分子作为对抗寄生虫的潜在效应物，如Gzma和Gzmb，它们在CX 3CR 1GFP/GFP单核细胞中升高。这些研究验证了肺蠕虫感染的双重先天细胞报告基因，并证明CX 3CR 1损害单核细胞-蠕虫相互作用。
Many helminth life cycles, including hookworm, involve a mandatory lung phase, where myeloid and granulocyte subsets interact with the helminth and respond to infection-induced lung injury. To evaluate these innate subsets, we employ Nippostrongylus brasiliensis infection of reporter mice for myeloid cells (CX3CR1GFP) and granulocytes (PGRPdsRED). Nippostrongylus infection induces lung infiltration of reporter cells, including CX3CR1+ myeloid cells and PGRP+ eosinophils. Strikingly, CX3CR1GFP/GFP mice, which are deficient in CX3CR1, are protected from Nippostrongylus infection with reduced weight loss, lung leukocyte infiltration, and worm burden compared to CX3CR1+/+ mice. This protective effect is specific for CX3CR1 as CCR2-deficient mice do not exhibit reduced worm burdens. Nippostrongylus co-culture with lung Ly6C+ monocytes or CD11c+ cells demonstrates that CX3CR1GFP/GFP monocytes secrete more proinflammatory cytokines, and actively bind the parasites causing reduced motility. RNA sequencing of Ly6C+ or CD11c+ cells shows Nippostrongylus-induced gene expression changes, particularly in monocytes, associated with inflammation, chemotaxis, and extracellular matrix remodeling pathways. We also identify cytotoxic and adhesion molecules as potential effectors against the parasite, such as Gzma and Gzmb, which are elevated in CX3CR1GFP/GFP monocytes. These studies validate a dual innate cell reporter for lung helminth infection and demonstrate that CX3CR1 impairs monocyte-helminth interaction.
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影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
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