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Luminal microvesicles uniquely influence translocating bacteria after SIV infection
Jacob K Flynn1, Charlotte A Langner1, Erik P Karmele2
1Barrier Immunity Section, Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Abstract:
Microbial translocation contributes to persistent inflammation in both treated and untreated HIV infection. Although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of Proteobacteria. We hypothesized that intestinal epithelial microvesicle cargo differs after HIV infection and contributes to biased translocation. We isolated gastrointestinal luminal microvesicles before and after progressive simian immunodeficiency virus (SIV) infection in rhesus macaques and measured miRNA and antimicrobial peptide content. We demonstrate that these microvesicles display decreased miR-28-5p, -484, -584-3p, and -584-5p, and let-7b-3p, as well as increased beta-defensin 1 after SIV infection. We further observed dose-dependent growth sensitivity of commensal Lactobacillus salivarius upon co-culture with isolated microvesicles. Infection-associated microvesicle differences were not mirrored in non-progressively SIV-infected sooty mangabeys. Our findings describe novel alterations of antimicrobial control after progressive SIV infection that influence the growth of translocating bacterial taxa. These studies may lead to the development of novel therapeutics for treating chronic HIV infection, microbial translocation, and inflammation.
Insights
HIV infection alters gut microvesicles, decreasing protective miRNAs and increasing antimicrobial peptides. This impacts bacterial growth, potentially driving inflammation and microbial translocation in HIV.
Area of Science:
- Microbiology
- Immunology
- Virology
Background:
- Microbial translocation, a key factor in HIV-associated inflammation, involves intestinal barrier dysfunction.
- A bias exists towards the translocation of Proteobacteria, suggesting specific mechanisms at play.
Purpose of the Study:
- To investigate if intestinal epithelial microvesicle cargo changes post-HIV infection and contributes to biased microbial translocation.
- To identify specific molecular differences in microvesicles that influence bacterial growth.
Main Methods:
- Isolation of gastrointestinal luminal microvesicles from rhesus macaques before and after simian immunodeficiency virus (SIV) infection.
- Measurement of microvesicle miRNA and antimicrobial peptide content.
- Co-culture experiments to assess the impact of microvesicles on commensal bacteria growth.
Main Results:
- SIV infection led to decreased levels of specific miRNAs (miR-28-5p, -484, -584-3p, -584-5p, let-7b-3p) and increased beta-defensin 1 in microvesicles.
- Isolated microvesicles from infected macaques showed dose-dependent inhibition of Lactobacillus salivarius growth.
- These changes were not observed in non-progressively infected sooty mangabeys.
Conclusions:
- Progressive SIV infection alters gut microvesicle composition, affecting antimicrobial control.
- These alterations influence the growth of bacterial taxa that may translocate across the gut barrier.
- Findings offer insights into novel therapeutic targets for HIV, microbial translocation, and chronic inflammation.
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