# Consequences of vaginal microbiota on IFNγ-mediated clearance of Chlamydia trachomatis

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $611,183

## Abstract

Chlamydia trachomatis (CT) infections are a major public health concern as they can adversely affect
female fertility and neonatal health. While natural history studies indicate that some women spontaneously clear
their infection, the physiological conditions that permit spontaneous clearance of CT remain elusive. Understand
the latter is key to developing an effective vaccine that to prevent CT infection and its devastating consequences.
In vitro and in vivo studies indicate that interferon gamma (IFNγ) is the primary protective cytokine against CT.
IFNγ induces the host enzyme indoleamine 2,3-dioxygenase (IDO1) that degrades tryptophan, an essential
amino acid for CT, which cannot synthesize tryptophan de novo. All clinical genital CT isolates have evolved a
mechanism to evade the effect of IFNγ, specifically they can express a functional tryptophan synthase that
salvages exogenously provided indole to generate tryptophan within the intracellular chlamydial inclusion where
it is impervious to IDO1. While neither CT, nor human cells, synthesize indole, some members of the vaginal
microbiome that increase greatly in number and proportion during bacterial vaginosis (BV), can do so. Thus, we
hypothesize that the composition of the vaginal microbiome, and its capacity to provide indole, modulates the
efficacy of IFNγ-dependent host immunity against CT. This hypothesis is supported by our existing clinical data;
although all women who spontaneously cleared CT infection had high endocervical IFNγ levels, so did ~40% of
women who failed to clear infection. We propose to rigorously test this hypothesis using a cohort of high-risk
African-American women attending our STD clinic in New Orleans. The cohort will be stratified into groups that
spontaneously clear CT infections (~28% in our cohort) or fail to clear CT infection between enrollment and
return-for-treatment visits. By focusing on women who spontaneously clear infection, and the ~40% of non-
clearing women who meet the threshold endocervical IFNγ levels observed in clearers, we will investigate the
following objectives: 1) Determine the infection micromilieu (tryptophan/indole/IFNγ/CT load & gene expression
profile) correlates of clearance; 2) Determine differences in the prevalent vaginal microbiome, and its indole-
generation capacity, between clearers and non-clearers; and 3) Using a novel endocervical epithelial cell model,
directly test the capacity of indole-producing microbiome members to limit IFNγ-mediated CT clearance, and
evaluate the efficacy of known small molecule indole biosynthesis inhibitors to augment IFNγ-mediated CT
clearance during co-infections. The outcomes from the proposed studies will provide essential information
needed to design novel immunological and pharmacological approaches that improve clinical outcomes for CT-
infected patients. Modeling the mechanisms used during spontaneous clearance will define the effects of co-
infection on the efficacy of the host response...

## Key facts

- **NIH application ID:** 9971343
- **Project number:** 5R01AI118860-04
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Ashok A Aiyar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,183
- **Award type:** 5
- **Project period:** 2017-08-08 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971343

## Citation

> US National Institutes of Health, RePORTER application 9971343, Consequences of vaginal microbiota on IFNγ-mediated clearance of Chlamydia trachomatis (5R01AI118860-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971343. Licensed CC0.

---

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