# Polymicrobial Context of Neisseria gonorrhoeae Infection and Mucosal Immune Response

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $187,499

## Abstract

PROJECT SUMMARY/ABSTRACT
Neisseria gonorrhoeae is a Gram-negative bacterium that causes the sexually transmitted infection (STI)
gonorrhea. With an estimated 78 million cases of gonorrhea annually worldwide, increasing frequency of
resistance to all recommended antibiotics, and the lack of a protective vaccine, N. gonorrhoeae is a prominent
and growing threat to human health. In women, N. gonorrhoeae establishes infection at the cervix, where it
initiates an inflammatory response characterized by the local recruitment of neutrophils. Viable N. gonorrhoeae
are recovered from human gonorrheal exudates, indicating that neutrophils cannot effectively clear infection.
The resulting cycle of sustained infection and neutrophilic inflammation enables N. gonorrhoeae transmission as
well as ascending infection and tissue damage, which underlie sequelae such as pelvic inflammatory disease,
ectopic pregnancy, and infertility. Moreover, infection with N. gonorrhoeae is highly epidemiologically associated
with coinfection with Chlamydia trachomatis, enhancing likelihood of these negative consequences. Identifying
the mechanisms underlying cervical infection and inflammation by these prominent STI pathogens is critical for
finding new therapeutic approaches to enhance women’s overall health and reproductive fitness. Our knowledge
of the bacterial and host conditions that facilitate productive N. gonorrhoeae infection in women is hampered by
the absence of a robust model for human genital infection that incorporates resident and recruited host cells,
maintains the architecture of the lower female genital tract, and incorporates the genital microbiota. To overcome
this knowledge gap, we will use the 3D human primary cervicovaginal biomimetic system developed by our group
to answer fundamental questions about the biology of female genital infection, alone and in the context of
cervicovaginal microbiota that we hypothesize are associated with susceptibility (bacterial vaginosis-associated
anaerobes, community state type-IV) and resistance (Lactobacillus crispatus-dominant, community state type-
I). Aim 1 will define the influence of the microbiota on the progression of cervicovaginal N. gonorrhoeae infection
and effects on epithelial host defenses. Aim 2 will characterize the effect of the microbiota on the cervicovaginal
recruitment of immune cells in response to N. gonorrhoeae. Aim 3 will define how coinfection with N. gonorrhoeae
and C. trachomatis in the context of the microbiota impacts pathogen burden and cervicovaginal immune
response. These studies will include vaginal and endocervical cells from women along with their autologous
microbiota, as well as unmatched microbiota, to evaluate how the host-microbiota interaction influences the
progression and outcome of infections. The findings arising from these studies about the infection process and
ensuing inflammatory response and tissue integrity can reveal new interventions to limit bacterial load and
mucosa...

## Key facts

- **NIH application ID:** 10190236
- **Project number:** 1U19AI158930-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Alison K Criss
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $187,499
- **Award type:** 1
- **Project period:** 2021-04-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190236

## Citation

> US National Institutes of Health, RePORTER application 10190236, Polymicrobial Context of Neisseria gonorrhoeae Infection and Mucosal Immune Response (1U19AI158930-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10190236. Licensed CC0.

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