生物
免疫学
先天免疫系统
归巢(生物学)
人类免疫缺陷病毒(HIV)
免疫系统
TLR4型
病毒学
先天性淋巴细胞
炎症
医学
微生物学
生态学
作者
Allen Ka Loon Cheung,Hauyee Kwok,Yiru Huang,Min Chen,Yufei Mo,Xilin Wu,Ka-shing Lam,Hoi-Kuan Kong,Terrence Chi‐Kong Lau,Jingying Zhou,Jingjing Li,Lin Cheng,Boon Kiat Lee,Qiaoli Peng,Xiaofan Lu,Minghui An,Hui Wang,Hong Shang,Boping Zhou,Hao Wu,Aimin Xu,Kwok‐Yung Yuen,Zhiwei Chen
出处
期刊:Nature microbiology
日期:2017-08-14
卷期号:2 (10): 1389-1402
被引量:14
标识
DOI:10.1038/s41564-017-0006-5
摘要
The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1-TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.
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