Longer neutrophil lifespan may contribute to HIV-associated intestinal inflammation

April 11, 2019

The increased survival of white blood cells called neutrophils is associated with alterations in the intestinal microbiome of HIV-infected individuals, according to a study published April 11 in the open-access journal PLOS Pathogens by Nichole Klatt of the University of Miami, and colleagues. Moreover, the findings suggest that Lactobacillus bacteria, which are commonly in probiotics, may reduce neutrophil lifespan, and could be an effective therapeutic strategy to reduce intestinal inflammation in HIV-infected individuals.

HIV infection results in chronic immune activation that leads to increased risk of other diseases and premature death, and this has been linked to gastrointestinal damage in infected individuals. Pathogen-fighting immune cells called neutrophils have been implicated in tissue damage in other gastrointestinal diseases, but it has not been clear whether neutrophils contribute to gastrointestinal damage in HIV infection. In the new study, Klatt and colleagues addressed this gap in knowledge by quantifying neutrophils in relation to other white blood cells in the gastrointestinal tissues of HIV-infected individuals receiving treatment.

The findings show that neutrophils in the gastrointestinal tract of HIV-infected individuals have a longer lifespan. Therefore, increased neutrophil lifespan may contribute to neutrophil accumulation in colorectal biopsy tissue, potentially implicating neutrophil lifespan as a new therapeutic target for intestinal inflammation in HIV infection. The results also suggest that different bacteria that naturally reside in the gastrointestinal tract can alter neutrophil lifespan, and that changes in the relative abundances of these bacteria in HIV infection may contribute to increased neutrophil lifespan. Specifically, Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

"These data were so striking because that they clearly implicate neutrophil lifespan as a potential target to reduce intestinal inflammation in HIV infection," notes Klatt. "Neutrophil lifespan is increased in many different chronic diseases, and strategies targeting neutrophil lifespan are being investigated to reduce neutrophil-driven inflammation. However, this connection had not previously been investigated in the context of HIV infection."

"I think one of the most exciting and interesting findings was that Lactobacillus species can override neutrophil survival signals and reduce neutrophil lifespan and numbers," states first author Tiffany Hensley-McBain. "Overall, we believe these data have important and widespread implications for discovering new therapeutics for neutrophil-driven inflammation in not only HIV infection, but many chronic inflammatory diseases."
Research Article

Funding: This work was supported by start-up funds to NRK from University of Washington and Washington National Primate Research Center and by National Institutes of Health award numbers NIH/NIDDK RO1DK112254 and NIH/NIDA 1DP13A037979 to NRK. Additional support was provided by the University of Washington Center for AIDS Research, which is funded by the National Institutes of Health under award number AI027757, and the National Institutes of Health, Office of the Director through P51OD010425-56 (MG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Hensley-McBain T, Wu MC, Manuzak JA, Cheu RK, Gustin A, Driscoll CB, et al. (2019) Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection. PLoS Pathog 15(4): e1007672. https://doi.org/10.1371/journal.ppat.1007672

Author Affiliations:

Department of Pharmaceutics, University of Washington, Seattle, WA, United States of America, Washington

National Primate Research Center, Seattle, WA, United States of America

Biostatistics and Biomathematics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America

Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL, United States of America

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA, United States of America

Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, United States of America

National HIV and Retrovirology Labs, Public Health Agency of Canada, Winnipeg, Manitoba, Canada

Departments of Obstetrics & Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden

Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America

Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America

Department of Medicine, University of Washington, Seattle, WA, United States of America


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