Tuesday, March 17, 2026 3/17/2026

Interferon-inducible cell-intrinsic host defense against Chlamydia trachomatis

Award Number: R37AI103197
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2013
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Interferon-inducible cell-intrinsic host defense against Chlamydia trachomatis - Chlamydia trachomatis is the cause for the most common bacterial sexually transmitted infection. Commonly referred to as a silent epidemic, C. trachomatis infections in women frequently manifest with subclinical inflammation, and therefore often go unnoticed and untreated. The infection can persist for months or years and ultimately cause pelvic inflammatory disease, ectopic pregnancies, and infertility. In order to establish persistent infections, C. trachomatis must subvert both the innate and the adaptive branches of the immune system. A central node that connects adaptive and innate immunity to C. trachomatis is the cytokine gamma-interferon (IFN). This cytokine is produced by innate (ILCs) and adaptive lymphocytes (T cells) and induces cell-autonomous immunity against Chlamydia in epithelial cells. To overcome IFN-mediated immunity and replicate inside human epithelial cells, C. trachomatis evolved counter-defenses specifically adapted to its human host. These C. trachomatis counter-defenses and the corresponding repertoire of IFN-inducible anti-Chlamydia defense programs are poorly characterized. Our goal is to decipher this antagonistic interplay between IFN-mediated host defense and chlamydial counter- defense. We perform unbiased functional genomics screens to identify human IFN-inducible genes (ISGs) that exert potent anti-Chlamydia defenses. In parallel we employ defined C. trachomatis mutant libraries in functional bacterial genetic screens to identify C. trachomatis genes that subvert ISG-driven defense pathways. Taking these approaches, we identified the ubiquitin E3 ligase RNF213 as a human ISG that eliminates non-human-adapted Chlamydia from human cells through a novel and uncharacterized innate immune pathway. Reciprocally, we identified the secreted C. trachomatis virulence factor GarD as an RNF213 antagonist protecting C. trachomatis from RNF213-driven cell-autonomous immunity in human cells. The mechanism by which this newly discovered RNF213-mediated cell-autonomous defense program eliminates vacuolar pathogens such as C. trachomatis garD mutant is unknown and will be interrogated through multidisciplinary approaches in this proposal. Complementary to these studies dissecting RNF213’s host defense function, we will identify and characterize additional RNF213-independent human cell- autonomous immune programs directed at Chlamydia and the corresponding counter-immune strategies employed by C. trachomatis. Using organoid and traditional human cell culture systems as well as novel in vivo mouse models, we will interrogate the importance of these antagonist host-pathogen relationships in immune clearance and immunopathology of Chlamydia infections. Such novel insights may guide the development of new therapeutic or prophylactic treatments or vaccine designs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $541,485 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	13	12/24/2025	NON-COMPETING CONTINUATION	$541,485
														Subtotal = $541,485

Issue Date FY: 2025 ( Subtotal = $541,485 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	12	12/16/2024	NON-COMPETING CONTINUATION	$541,485
														Subtotal = $541,485

Issue Date FY: 2024 ( Subtotal = $541,485 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	002	11	9/3/2024	COMPETING CONTINUATION	$55,697
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	11	8/29/2024	COMPETING CONTINUATION	$0
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	11	11/14/2023	COMPETING CONTINUATION	$485,788
														Subtotal = $541,485

Grand Total All Awards = $1,624,455

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Interferon-inducible cell-intrinsic host defense against Chlamydia trachomatis

Award Number: R37AI103197

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/15/2013

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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