# Impact of Microbial Dysbiosis on MAIT Cell Tissue Repair Program after Acute HIV Infection

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $256,932

## Abstract

Project Summary / Abstract
Mucosa-associated invariant T-cells (MAIT) are a subset of unconventional, innate-like T cells that are highly
abundant in mucosal tissues and peripheral blood and recognize microbial vitamin B2 (riboflavin) metabolites
from a wide range of microbes. Furthermore, MAIT cells have been recently shown to have tissue repair
functions. In HIV infection, MAIT cells are irreversibly lost in the blood and gut, and remaining cells display
elevated signs of activation with decreased functional potential. Another consequence of HIV is a profound
dysbiosis of the gut microbiome characterized by reshaped abundances of commensals turned pathogenic. HIV-
associated compromised gut mucosal immunity is thought to be a major driver of persistent immune activation,
viral replication, and morbidity and mortality, even in individuals who are on effective ART. Studies show that
chronic HIV infection is associated with reduced gut bacterial diversity and an enrichment in fusobacteria,
associated with reduced T cell counts and higher inflammation. Yet, the etiology of dysbiosis in HIV infection
remains unclear. We have an unprecedented opportunity to address this significant gap in knowledge by
leveraging matched biospecimens of gut tissue biopsies and peripheral blood mononuclear cells (PBMCs) from
treatment naïve and ART-treated acutely and chronically HIV infected individuals enrolled in an observational
HIV study in Thailand. Because of associations with gut integrity and control of microbial infections, the
dysfunction of MAIT cells in HIV-1 infection may leave the host with weakened mucosal and antimicrobial
immunity. To date, no studies have linked MAIT cells with surrogates of gut integrity, microbial translocation, or
specific makeup of the microbiota in gut tissue during HIV infection. The overall goals of the project are to: (a)
determine if imbalance in the normal gut microbiota impacts MAIT cell frequency, phenotype, and tissue repair
function across stages of HIV infection; and (b) to ascertain if ART initiated early in acute HIV infection alters the
relationship between the initial perturbations of the gut microbiota and the early engagement of the MAIT cell
compartment. In AIM 1, we will perform MAIT cell and microbiome analysis on matched PBMCs and plasma
samples from treatment naïve acutely HIV infected individuals, and HIV uninfected healthy controls matched for
age and gender. We will examine if increases in translocated fusobacteria are associated with change in MAIT
cells numbers and activation in the blood and gut. We will investigate if HIV-induced dysfunction of MAIT cells is
associated with markers of reduced gut barrier integrity. In AIM 2, we will use PBMCs and plasma samples from
uninfected and HIV-infected individuals that initiated treatment at different stages of acute infection to evaluate
the impact of ART initiation timing on microbial dysbiosis and MAIT cell tissue repair functions. In vitro
experiments will...

## Key facts

- **NIH application ID:** 10481899
- **Project number:** 1R21DK132985-01
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Michael Jay Corley
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $256,932
- **Award type:** 1
- **Project period:** 2022-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481899

## Citation

> US National Institutes of Health, RePORTER application 10481899, Impact of Microbial Dysbiosis on MAIT Cell Tissue Repair Program after Acute HIV Infection (1R21DK132985-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10481899. Licensed CC0.

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