Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.
Hensley-McBain T, Wu MC, Manuzak JA, Cheu RK, Gustin A, Driscoll CB, Zevin AS, Miller CJ, Coronado E, Smith E et al.
PLoS Pathog. Apr 2019. doi: 10.1371/journal.ppat.1007672
COMMENT: In this work the authors investigate about the gastrointestinal dysfunction in HIV patients focusing on the role of neutrophils and on the possible involvement of the intestinal microbiome in the neutrophil-driven inflammation. The authors propose to use the ability of some commensal bacteria to reduce neutrophil accumulation and tissue damage in HIV infection and to apply the same kind of strategy for other inflammatory conditions.
This is the hypothesis that the authors propose:
In this study, we hypothesized that HIV-infected individuals would have increased neutrophil frequencies in the lower GI with reduced neutrophil apoptosis. We further hypothesized that different bacterial species would differentially contribute to alterations in neutrophil apoptosis.
These are the flow cytometry assays for quantifies the neutrophil frequencies done in this work:
Colorectal biopsies from a total of 40 HIV-infected, ART-suppressed individuals and 35 HIV-uninfected individuals were collected for this study. Of these colorectal biopsy samples, neutrophil frequencies were assessed by flow cytometry in real-time in 23 HIV-infected, ART-suppressed and 25 HIV-uninfected participants.
These were the main findings about the quantification of neutrophils:
We found increased neutrophil frequencies in the GI of HIV+ individuals compared to uninfected controls
... we found that the frequency of these surviving, functional neutrophils was increased in biopsies from HIV+ individuals compared to uninfected controls
16S taxonomic profiling analysis was carried out to investigate special features in HIV infected patients:
... we assessed the mucosal microbiome composition by 16S rRNA gene sequencing of colorectal biopsies collected from all 40 HIV-infected, ART-suppressed individuals and all 35 HIV-uninfected individuals. We focused on bacterial composition at both the family and genus taxonomic levels and observed a modest significant association between overall microbial composition at the genus level and HIV status when HIV-infected, ARTsuppressed individuals were compared to uninfected controls
They found that the Lactobacillus:Prevotella ratio was different in the HIV-infected set of patients:
Lactobacillus:Prevotella ratio associates with GI Neutrophil survival in vivo we observed a significant difference in the ratio of Lactobacillus:Prevotella between HIV-infected, ART-suppressed and uninfected individuals, suggesting an altered balance of these genera
And then they studied Lactobacillus species and their impact in neutrophil survival
... we examined the ability of bacterial ligands and various whole bacteria to impact neutrophil survival in an in vitro culture system with whole blood.
All bacterial species significantly increased neutrophil survival after incubation with whole blood, with the exception of Lactobacillus species Importantly, Lactobacillus plantarum and Lactobacillus rhamnosus decreased neutrophil survival. Additionally, we found that both Lactobacillus species decreased total neutrophil frequencies
Neutrophil apoptosis has emerged as a therapeutic target for the resolution of acute and chronic inflammation in the lungs, the intestines, and arthritis but no strategies are approved for use in humans to-date. Here, we provide evidence that this may also be a therapeutic target to reduce intestinal inflammation in HIV-infected individuals by demonstrating increased GI neutrophil survival in HIV infection.
Finally, these data lead to new avenues of research whereby commensal bacteria, their surface antigens, and their products should be further assessed for their therapeutic ability to reduce neutrophil accumulation and tissue damage in HIV infection and other inflammatory conditions.