Gut-homing Δ42PD1 + Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection.

Autor: Cheung AKL; 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., Kwok HY; 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., Huang Y; 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., Chen M; 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.; Yunnan Center for Disease Control and Prevention, 650000, Kunming, Yunnan Province, China., Mo Y; 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., Wu X; 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., Lam KS; 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., Kong HK; Department of Biomedical Sciences, City University of Hong Kong, 999097, Hong Kong SAR, China., Lau TCK; Department of Biomedical Sciences, City University of Hong Kong, 999097, Hong Kong SAR, China., Zhou J; 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., Li J; 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., Cheng L; 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.; 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., Kiat Lee B; 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., Peng Q; 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., Lu X; 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., An M; 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., Wang H; 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., Shang H; 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., Zhou B; 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., Wu H; 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., Xu A; 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., Yuen KY; 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., Chen Z; 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. zchenai@hku.hk.; 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. zchenai@hku.hk.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2017 Oct; Vol. 2 (10), pp. 1389-1402. Date of Electronic Publication: 2017 Aug 14.
DOI: 10.1038/s41564-017-0006-5
Abstrakt: 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.
Databáze: MEDLINE
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