Patients being treated for HIV can have more inflammation in their gastrointestinal tract although the reasons for this were unclear. New research published in Plos Pathogens has shown that the effect is likely caused by the increased lifespan of neutrophils in the gut. The research team from the US led by Nichole Klatt took samples from patients and used flow cytometry to measure the lifespan of neutrophils.
"These data were so striking because 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."
A key finding in the paper was the interaction between the neutrophils and the gut microbiota. The team found that patients with with HIV tended to have a lower Lactobacillus:Prevotella ratio indicating HIV infection has an effect on the gut flora. This led to the hypothesis that probiotics could be a treatment for the GI tract inflammation. The researchers tested this hypothesis in vitro and found that Lactobacillus species increased neutrophil apoptosis and decreased their overall lifespan.
"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."
Read the full paper here.
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.
Tiffany Hensley-McBain, Michael C. Wu, Jennifer A. Manuzak, Ryan K. Cheu, Andrew Gustin, Connor B. Driscoll, Alexander S. Zevin, Charlene J. Miller, Ernesto Coronado, Elise Smith, Jean Chang, Michael Gale Jr., Ma Somsouk, Adam D. Burgener, Peter W. Hunt, Thomas J. Hope, Ann C. Collier, Nichole R. Klatt. (2019). PLOS Pathogens. Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection
Published: April 11, 2019 https://doi.org/10.1371/journal.ppat.1007672