CCR2+ Inflammatory Monocytes Are Recruited to Yersinia pseudotuberculosis Pyogranulomas and Dictate Adaptive Responses at the Expense of Innate Immunity during Oral Infection.
CCR2+ Inflammatory Monocytes Are Recruited to Yersinia pseudotuberculosis Pyogranulomas and Dictate Adaptive Responses at the Expense of Innate Immunity during Oral Infection.
复制标题
CCR2 炎症单核细胞被招募到假结核耶尔森菌脓性肉芽肿中，并在口腔感染期间以牺牲先天免疫为代价来指示适应性反应。
DOI：
10.1128/iai.00782-17
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发表时间：
2018
影响因子：
3.1
通讯作者：
Bliska,JamesB
中科院分区：
文献类型：
--
作者：
Zhang,Yue;Khairallah,Camille;Sheridan,BrianS;vanderVelden,AdrianusWM;Bliska,JamesB
鼠Ly 6Chi炎性单核细胞（IM）需要CCR 2离开骨髓并进入肠系膜淋巴结（MLN）和其他器官以响应假结核耶尔森氏菌感染。我们正在研究可以分化为CD 11 c+树突状细胞（DC）的IM如何促进对Y的先天性和适应性免疫。假结核以前，我们获得的证据表明，IM是重要的显性CD 8 +T细胞的表位YopE 69 - 77的反应和宿主的生存使用减毒Y静脉感染。假结核在这里，我们用野生型Y经口攻击CCR 2 +/+或CCR 2 −/−小鼠。假结核研究如何IM有助于肠道感染期间的免疫反应。出乎意料的是，CCR 2 −/−小鼠的存活率没有降低，但体重保持得更好，而且它们的MLN清除了Y。与对照组相比，假结核更快，淋巴结病减少。CCR 2-GFP小鼠MLN和脾脏的原位成像显示，绿色荧光蛋白阳性（GFP+）IM聚集在富含嗜中性粒细胞的耶尔森氏菌脓肉芽肿周围。GFP+ IM与MLN中的CD 11 c+细胞和YopE 69 -77特异性CD 8 +T细胞共定位，表明IM衍生的DC在耶尔森氏脓癣肉芽肿中引发适应性应答。一致地，CCR 2 −/−小鼠的脾脏DC、YopE 69 -77特异性CD 8 +T细胞、CD 4 +T细胞和器官中的B细胞数量减少，血清抗Y细胞抗体水平降低。假结核抗原我们的数据表明，在MLN脓肉芽肿中，IM分化为DC，并在口服Y。假结核感染
Murine Ly6Chiinflammatory monocytes (IMs) require CCR2 to leave the bone marrow and enter mesenteric lymph nodes (MLNs) and other organs in response to Yersinia pseudotuberculosis infection. We are investigating how IMs, which can differentiate into CD11c+dendritic cells (DCs), contribute to innate and adaptive immunity to Y. pseudotuberculosis. Previously, we obtained evidence that IMs are important for a dominant CD8+T cell response to the epitope YopE69–77and host survival using intravenous infections with attenuated Y. pseudotuberculosis. Here we challenged CCR2+/+or CCR2−/−mice orally with wild-type Y. pseudotuberculosis to investigate how IMs contribute to immune responses during intestinal infection. Unexpectedly, CCR2−/−mice did not have reduced survival but retained body weight better and their MLNs cleared Y. pseudotuberculosis faster and with reduced lymphadenopathy compared to controls. Enhanced bacterial clearance in CCR2−/−mice correlated with reduced numbers of IMs in spleens and increased numbers of neutrophils in livers.In situimaging of MLNs and spleens from CCR2-GFP mice showed that green fluorescent protein-positive (GFP+) IMs accumulated at the periphery of neutrophil-rich Yersinia-containing pyogranulomas. GFP+IMs colocalized with CD11c+cells and YopE69–77-specific CD8+T cells in MLNs, suggesting that IM-derived DCs prime adaptive responses in Yersinia pyogranulomas. Consistently, CCR2−/−mice had reduced numbers of splenic DCs, YopE69–77-specific CD8+T cells, CD4+T cells, and B cells in organs and lower levels of serum antibodies to Y. pseudotuberculosis antigens. Our data suggest that IMs differentiate into DCs in MLN pyogranulomas and direct adaptive responses in T cells at the expense of innate immunity during oral Y. pseudotuberculosis infection.