Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS Pathog. 2014 Dec 11;10(12):e1004543. doi: 10.1371/journal.ppat.1004543. eCollection 2014.

Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation.

Author information

  • 1Department 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.
  • 2AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, Maryland, United States of America.
  • 3Clinical and Molecular Retrovirology Section/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 4Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • 5SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
  • 6Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
  • 7Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 8U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
  • 9SEARCH, Bangkok, Thailand.
  • 10Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand; SEARCH, Bangkok, Thailand.
  • 11Virus 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.
  • 12Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
  • 13Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; SEARCH, Bangkok, Thailand; The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
  • 14SEARCH, Bangkok, Thailand; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
  • 15Henry M. Jackson Foundation for the Advancement of Military Medicine, 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.

Abstract

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.

PMID:
25503054
PMCID:
PMC4263756
DOI:
10.1371/journal.ppat.1004543
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center