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PLoS Pathog. 2019 Apr 11;15(4):e1007672. doi: 10.1371/journal.ppat.1007672. eCollection 2019 Apr.

Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.

Author information

1
Department of Pharmaceutics, University of Washington, Seattle, WA, United States of America.
2
Washington National Primate Research Center, Seattle, WA, United States of America.
3
Biostatistics and Biomathematics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
4
Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL, United States of America.
5
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA, United States of America.
6
Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, United States of America.
7
National HIV and Retrovirology Labs, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
8
Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
9
Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
10
Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
11
Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
12
Department of Medicine, University of Washington, Seattle, WA, United States of America.

Abstract

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

PMID:
30973942
DOI:
10.1371/journal.ppat.1007672
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Conflict of interest statement

The authors have declared that no competing interests exist.

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