# Microbial and innate immune mechanisms of oral inflammation during SIV infection

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $433,664

## Abstract

HIV/SIV infections lead to a breakdown of the integrity of the epithelial mucosa resulting in severe microbial
dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one
of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression can
result in candidiasis, necrotizing gingivitis, periodontitis, hairy leukoplakia, increased oral tumors, and can also
contribute to and predict distal disease complications elsewhere. RORγt+ innate lymphoid cells type 3 (ILC3)
produce IL-17 and IL-22 and are vital for maintaining the integrity of the GI epithelium, mediating mucosal
antimicrobial defense and stability of commensal microflora, but others and we have recently shown massive,
systemic alterations in ILC3 numbers and functions in the oral, reproductive and gastrointestinal mucosae (Li
and Reeves, Front Immunol, 2013; Li et al., PLoS Path, 2014). Furthermore, in our unpublished preliminary
data we show: 1. SIV infection induces a highly inflammatory and cytotoxic ILC3 phenotype in the oral cavity;
2. Efficient depletion in oral, colorectal, and vaginal mucosae using a novel ILC3-depleting antibody developed
by our laboratory specifically for rhesus macaques. 3. Dysbiosis of specific microbial species is associated with
chronic immune activation; and 4. Probiotic therapy reduces immune activation during SIV infection and
induces expansion of functional ILC3 numbers in the mucosae. In this innovative and transformative proposal
we will evaluate the core hypothesis that ILC3 act as a sensitive and targetable modulator for mucosal
homeostasis, immune activation, and microflora in the oral cavity through three complementary specific aims:
1. Experimentally determine the role of ILCs in modulating the oral microbiome and oral mucosae
homeostasis; 2. Define the kinetics, activation, and detailed immunologic effects of SIV infection on
ILCs and microbiome in the oral cavity; and 3. Investigate the effects of probiotic therapy on oral ILCs
and microbiome during chronic treated and untreated SIV infection.

## Key facts

- **NIH application ID:** 9933884
- **Project number:** 5R01DE026327-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Roger Keith Reeves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,664
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-06-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933884

## Citation

> US National Institutes of Health, RePORTER application 9933884, Microbial and innate immune mechanisms of oral inflammation during SIV infection (5R01DE026327-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9933884. Licensed CC0.

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