机构：[1]AIDS Institute, Research Center for Infection and Immunity, Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, 999097 Hong Kong SAR, China.[2]Yunnan Center for Disease Control and Prevention, 650000 Kunming, Yunnan Province, China.[3]Department of Biomedical Sciences, City University of Hong Kong, 999097 Hong Kong SAR, China.[4]HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People’s Hospital, 518000 Shenzhen, China.[5]STD/HIV Research Laboratory and Department of Infectious Diseases, Beijing Key Laboratory of HIV/AIDS Research, Beijing You-An Hospital, Capital Medical University, 100000 Beijing, China.[6]Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, China Medical University, 110000 Shenyang, China.[7]Department of Pharmacology & Pharmacy and Department of Medicine, Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, 999097 Hong Kong SAR, China
The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a V delta 2 subset of gut-homing gamma delta T cells with significantly upregulated Delta 42PD1 (a PD1 isoform) in acute (similar to 20%) HIV-1 patients compared to chronic HIV-1 patients (similar to 11%) and healthy controls (similar to 2%). The frequency of Delta 42PD1(+)V delta 2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Delta 42PD1 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 Delta 42PD1(+)V delta 2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Delta 42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Delta 42PD1 or TLR4 successfully reduced the cytokine effect induced by Delta 42PD1(+)V delta 2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Delta 42PD1-TLR4 pathway exhibited by virus-induced gut-homing V delta 2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Delta 42PD1(+)V delta 2 cells may serve as a target for the investigation of diseases with mucosal inflammation.
基金：
This work was supported by research grants from the Hong Kong Research Grant Council (RGC: HKU5/
CRF/13G, RGC17103514, RGC17122915 and A-HKU709/14 to Z.C.); the Health and
Medical Research Fund (HMRF: 14130582 to Z.C., 15140372 to A.K.L.C.); the San-
Ming Project of Medicine in Shenzhen (to Z.C. and H.Wa.); the National Science and
Technology Major Project (2012ZX10001-009-001-001 to Z.C., 2012ZX1000-1006-
001-009 to H.S.) Beijing Key Laboratory of HIV/AIDS Research (BZ0089 to H.Wu)
and Beijing Municipal of Science and Technology Major Project (D161100000416003
to H.Wu) and the University Development Fund of the University of Hong Kong and
Li Ka Shing Faculty of Medicine Matching Fund to AIDS Institute.
第一作者机构：[1]AIDS Institute, Research Center for Infection and Immunity, Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, 999097 Hong Kong SAR, China.
通讯作者：
通讯机构：[1]AIDS Institute, Research Center for Infection and Immunity, Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, 999097 Hong Kong SAR, China.[4]HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People’s Hospital, 518000 Shenzhen, China.
推荐引用方式(GB/T 7714)：
Allen Ka Loon Cheung,Hau-yee Kwok,Yiru Huang,et al.Gut-homing Delta 42PD1(+)V delta 2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection[J].NATURE MICROBIOLOGY.2017,2(10):1389-1402.doi:10.1038/s41564-017-0006-5.
APA：
Allen Ka Loon Cheung,Hau-yee Kwok,Yiru Huang,Min Chen,Yufei Mo...&Zhiwei Chen.(2017).Gut-homing Delta 42PD1(+)V delta 2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection.NATURE MICROBIOLOGY,2,(10)
MLA：
Allen Ka Loon Cheung,et al."Gut-homing Delta 42PD1(+)V delta 2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection".NATURE MICROBIOLOGY 2..10(2017):1389-1402
生物学