Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

PLoS Pathogens

Irini Sereti¹  Suchada Sukhumvittaya¹  Rungsun Rerknimitr²  Nittaya Phanuphak³  Jintanat Ananworanich³  Rapee Trichavaroj⁴  Netanya G. Sandler⁴  Robert J. O′Connell⁴  Nelson L. Michael⁴  Jean-Louis Excler⁴  Surat Jongrakthaitae⁴  Eugene Kroon⁴  Alexandra Schuetz⁴  James L. K. Fletscher⁴  Claire Deleage⁵  Jerome H. Kim⁵  Praphan Phanuphak⁶  Mary Marovich⁶  Yuwadee Phuang-Ngern⁷  Robin Dewar⁷  Nitiya Chomchey⁷  Viseth Ngauy⁷  on behalf of the RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups⁷  Jacob D. Estes⁸  Merlin L. Robb⁸  Mark S. de Souza⁹  Siriwat Akapirat⁹  Daniel C. Douek^1,10 

[1] AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, Maryland, United States of America;Clinical and Molecular Retrovirology Section/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;Department of Retrovirology, Armed Forces Research Institute of Medical Sciences – United States Component, Bangkok, Thailand;Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America;Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;SEARCH, Bangkok, Thailand;The Thai Red Cross AIDS Research Centre, Bangkok, Thailand;U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America;Virus Isolation and Serology Laboratory Applied and Developmental Research Directorate Science Applications International Corporation, Frederick, Inc. National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, United States of America

关键词: Colon;    HIV;    HIV infections;    Cytotoxic T cells;    Immune activation;    T cells;    Blood;    Cell staining;   

DOI  :  10.1371/journal.ppat.1004543

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.

【 授权许可】

CC BY