# Role of Innate Immunity and Microbiome in the Inflammation of Aging and Long-Term Antiretroviral Therapy

> **NIH NIH P20** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $302,596

## Abstract

Role of Innate Immunity and Microbiome in the Inflammation of Aging and Long-Term Antiretroviral
Therapy
Summary
Inflammaging, characteristic of persistent systemic inflammation in the aging population, has been linked to
frailty syndrome with increased risk of cardiovascular disease, impaired mobility, cancer, cognitive decline, and
immunosenescence. Similarities between inflammaging and the course of treated HIV infections, including
chronic inflammation associated with gut epithelial barrier damage and microbial translocation, suggest that
HIV infection compresses the aging process, accelerating the development of comorbidities and frailty. Type-
17 immune cells that express the transcription factor RORγt and type-17 cytokines (IL17A, IL22, etc.) are
critical for a healthy gut barrier function and maintenance of mucosal immune and microbial homeostasis, and
function by stimulating neutrophil recruitment, epithelial cell proliferation, production of tight junction proteins
and anti-microbial defensins. Others and we have found that innate CD161+ T cells are a potent source of IL-
17 and are enriched in the gut mucosa. The first goal of this study is to determine the relationship of systemic
inflammation with the functions of innate type-17 immune cells (including innate T cells and innate lymphoid
cells) and the gut microbial composition. Utilizing the rhesus macaque model that most closely resembles
human aging as well as HIV-AIDS, it will be examined whether plasma biomarkers of inflammation are
associated with the immune signature of innate type-17 cells and fecal microbiome in aging vs. young adult
macaques. This will help describe an inflammaging phenotype based on inflammation-associated gut mucosal
immune signature and microbiome of aging macaques. The second goal is to establish whether long-term ART
in young adult macaques with or without SIV infection leads to inflammaging-associated perturbations in gut
mucosal innate type-17 immunity and microbiome. This will establish whether similar or synergistic immune
mechanisms of perturbations in gut mucosal homeostasis contribute to the phenomenon of accelerated aging
in treated HIV infections and determine the factors associated with the inflammaging phenotype in long-term
ART. These studies are relevant because they focus on understanding the immune mechanisms underlying
inflammaging and HIV/ART-associated inflammation and whether HIV/ART-associated inflammation is
accelerating the inflammaging process. The results of this study will provide valuable insights into the role of
gut mucosal type-17 cells and its microbiome in local and systemic inflammation of aging and ART. This will
open new avenues to explore the development of applications aimed at modulating mucosal innate immune
cells along with probiotics to reduce inflammaging and the risk of frailty syndrome in aging and treated HIV
infections.

## Key facts

- **NIH application ID:** 9932385
- **Project number:** 5P20GM103629-09
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Namita Rout
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $302,596
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932385

## Citation

> US National Institutes of Health, RePORTER application 9932385, Role of Innate Immunity and Microbiome in the Inflammation of Aging and Long-Term Antiretroviral Therapy (5P20GM103629-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9932385. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
