# Chlamydia pathogenesis

> **NIH NIH R56** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $570,684

## Abstract

Abstract
 Chlamydia pathogenesis
 Sexually transmitted infection with Chlamydia trachomatis (CT) is a leading infectious cause of tubal
infertility due to the induction of excessive fibrosis observed as adhesion and hydrosalpinx in the female upper
genital tract under laparoscopy. Both CT ascending infection and host immune responses likely contribute to
the sequelae. Intravaginal inoculation with Chlamydia muridarum (CM) induces hydrosalpinx in mice, which is
frequently used for investigating the pathogenic mechanisms of CT. The mouse model reveals a two-hit
mechanism for chlamydial induction of hydrosalpinx: The lower genital Chlamydia ascends to the upper genital
tract and infects oviduct epithelial cells, causing direct damages, as the 1st hit, and the Chlamydia-induced
lymphocytes with a profibrotic phenotype, after recruiting to the oviduct, may provide a 2nd hit to convert the
initial damage-triggered tissue repairing into pathological fibrosis. Both hits may be required for chlamydial
induction of the sequelae. CM that spreads from the genital tract to the gastrointestinal (GI) tract can most
efficiently induce pathogenic CD8+ T cells to provide a 2nd hit for promoting CM pathogenicity in the upper
genital tract of mice. Although CT is also frequently detected in the GI tract of women, it is unclear how CT
reaches the human GI tract and where CT induces 2nd hits for promoting CT pathogenicity in women.
Regardless of how a 2nd hit is induced, we hypothesize that chlamydial antigen-specific T lymphocytes,
particularly CD8+ T cells, are able to provide a 2nd hit for promoting chlamydial pathogenicity in the upper
genital tract by delivering profibrotic effectors. Since T cells are known to contribute to both chlamydial
pathogenesis and immunity, we further hypothesize that pathogenic and protective T cells may recognize both
common and distinct CT antigens. We will test these hypotheses by identifying profibrotic effectors of
pathogenic CD8+ T cells (Aim I), systematically mapping the antigen specificities of functionally defined
pathogenic vs. nonpathogenic CD8+ T cells from mice (Aim II) and identifying T cell antigens in CT-exposed
women with or without tubal infertility (Aim III). The information to be obtained will advance our understanding
of chlamydial pathogenic mechanisms and improve differential diagnosis of tubal infertility as well as facilitate
the development of Chlamydia subunit vaccines.

## Key facts

- **NIH application ID:** 10665396
- **Project number:** 1R56AI168279-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** GUANGMING ZHONG
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $570,684
- **Award type:** 1
- **Project period:** 2022-08-12 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665396

## Citation

> US National Institutes of Health, RePORTER application 10665396, Chlamydia pathogenesis (1R56AI168279-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10665396. Licensed CC0.

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