HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli.
HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli.
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DOI：
10.4049/jimmunol.1200681
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发表时间：
2012-07-15
期刊：
影响因子：
--
通讯作者：
Wilson CC
中科院分区：
文献类型：
--
作者：
Dillon SM;Manuzak JA;Leone AK;Lee EJ;Rogers LM;McCarter MD;Wilson CC
微生物易位与HIV-1疾病的全身免疫激活有关，但微生物促进HIV相关肠道发病的机制尚不清楚。重要的是，在HIV-1感染早期发生的持续病毒复制的背景下，我们对移位共生肠道细菌对粘膜相关T细胞反应的影响的了解有限。我们先前在正常人肠道固有层(Lp)中发现了大肠杆菌反应性T辅助细胞(Th)1和Th17细胞的共生。在这里，我们建立了一种体外实验来研究原代人类LP单个核细胞(LPMC)、共生大肠杆菌和CCR5嗜性HIV-1Bal中Th细胞亚群之间的相互作用。在暴露于HIV-1的LPMC中加入热灭活的大肠杆菌，可增加HIV-1的复制、CD4T细胞的激活和感染，以及IL-17和干扰素-γ的产生。相反，从共生菌中提取的纯化的脂多糖并不能增强CD4T细胞的感染。大肠埃希菌对LPMC Th17的刺激作用强于Th1细胞。在HIV-1暴露的LPMC培养中，Th17细胞比Th1细胞更容易感染，并且在大肠杆菌存在的情况下，Th17细胞的感染频率显著增加。大肠杆菌相关的感染增强依赖于CD11c+LP树突状细胞的存在，部分依赖于MHC第二类限制性抗原的呈递。这些结果突显了微生物移位在早期感染期间通过增加HIV-1复制和肠道Th1和Th17细胞的感染而影响粘膜HIV-1发病的潜在作用。
Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive T helper (Th)1 and Th17 cells in normal human intestinal lamina propria (LP). Here, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMC), commensal E. coli and CCR5-tropic HIV-1Bal. Addition of heat-killed E. coli to HIV-1-exposed LPMC resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1-exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, dependent on MHC Class II-restricted antigen presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.
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影响因子：
2.9
作者：
Gillevet, Patrick;Sikaroodi, Masoumeh;Keshavarzian, Ali;Mutlu, Ece A.
通讯作者：
Mutlu, Ece A.
影响因子：
5.4
作者：
Dillon, Stephanie M.;Friedlander, Laura J.;Wilson, Cara C.
通讯作者：
Wilson, Cara C.
影响因子：
6.4
作者：
Cassol, Edana;Malfeld, Susan;Rossouw, Theresa
通讯作者：
Rossouw, Theresa
影响因子：
9.1
作者：
Blaschitz, Christoph;Raffatellu, Manuela
通讯作者：
Raffatellu, Manuela
DOI：
10.1084/jem.20100090
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Geldmacher C;Ngwenyama N;Schuetz A;Petrovas C;Reither K;Heeregrave EJ;Casazza JP;Ambrozak DR;Louder M;Ampofo W;Pollakis G;Hill B;Sanga E;Saathoff E;Maboko L;Roederer M;Paxton WA;Hoelscher M;Koup RA
通讯作者：
Koup RA