Monday, June 30, 2025 6/30/2025

IL-17RA-signaling cytokines in the regulation of CD8 T cell immunity to T. cruzi

Award Number: R01AI110340
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: 03/01/2014
PERIOD OF PERFORMANCE END DATE: 02/29/2020

Group Awards By:

View Award Description

IL-17RA-signaling cytokines in the regulation of CD8 T cell immunity to T. cruzi - DESCRIPTION (provided by applicant): Chagas disease, caused by the parasite Trypanosoma cruzi, affects 8 million people and imposes a major economic burden due to early mortality and physical disabilities. It is endemic in Latin America but cases are increasing in non-endemic countries, becoming a global concern. Disease progression, from symptomless to severe, are linked to parasite heterogeneity and variable host immune response. Indeed, development of robust CD8+ T cell immunity is a key element of host resistance and T. cruzi persistence and chronic Chagas disease has been associated to suboptimal CD8+ T cell responses. Consequently, defining the nature of CD8+ T cells mediating immunoprotection and the rules governing the maintenance of these cells is crucial for our understanding of the pathogenesis of Chagas disease and also for the design of novel therapeutic and vaccination approaches. Cytokines are central environmental cues that dictate the magnitude and quality of protective CD8+ T cell responses and, thus, emerge as attractive targets for immunointervention. However, our incomplete knowledge about the cytokines, signaling pathways and transcriptional programs involved in the generation of optimal CD8+ T cell immunity holds back possible applications of relevance to human health. Our compelling preliminary findings show that IL-17RA-signaling cytokines are critically involved in the regulation of the developmental pathways that determine the generation of robust protective CD8+ T cell responses to T. cruzi. Using phenotypic, functional and genomic profiling we propose to dissect the mechanisms underlying IL-17RA-mediated regulation of specific CD8+ T cell development. Adoptive transfer experiments together with in vitro culture approaches will be used to establish whether IL-17RA-signaling plays CD8+ T cell intrinsic and/or extrinsic roles in supporting CD8+ T cell immunity. Finally, genetic vaccination and cytokine-based treatment will help to determine the potential therapeutic use of IL-17A to boost CD8+ T cell immunity to T. cruzi during natural infection and vaccination. Our studies will provide meaningful data about the role of IL-17RA-signaling cytokines in the regulation of CD8+ T cell immunity to T. cruzi, providing potential new targets for the rational design of therapies for Chagas disease and, likely, other chronic infections. We also expect to identify the cellular and molecular programs triggered by IL-17RA-signaling and how they dictate particular CD8+ T cell fates. This knowledge will profoundly impact on fundamental immunology and may provide a rationale for understanding unsuspected effects of IL-17-targeted therapies during human diseases.


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: 2020 ( Subtotal = $0 )
2020	2018	CONSEJO NACIONAL DE INVESTIGACIONES CIENTIFICAS Y TECNICAS	HAYA DE LA TORRE Y MEDINA ALLENDE, CIUDAD UNIVERSITARIA	CORDOBA	CORDOBA	X5000		ARG	Allergy and Infectious Diseases Research	000	5	7/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $133,640 )
2018	2018	CONSEJO NACIONAL DE INVESTIGACIONES CIENTIFICAS Y TECNICAS	HAYA DE LA TORRE Y MEDINA ALLENDE, CIUDAD UNIVERSITARIA	CORDOBA	CORDOBA	X5000		ARG	Allergy and Infectious Diseases Research	000	5	2/12/2018	NON-COMPETING CONTINUATION	$133,640
														Subtotal = $133,640

Issue Date FY: 2017 ( Subtotal = $133,640 )
2017	2017	CONSEJO NACIONAL DE INVESTIGACIONES CIENTIFICAS Y TECNICAS	HAYA DE LA TORRE Y MEDINA ALLENDE, CIUDAD UNIVERSITARIA	CORDOBA	CORDOBA	X5000		ARG	Allergy and Infectious Diseases Research	000	4	2/22/2017	NON-COMPETING CONTINUATION	$133,640
														Subtotal = $133,640

Issue Date FY: 2016 ( Subtotal = $133,400 )
2016	2016	CENTRO DE INVESTIGACIONES EN BIOQUIMICA CLINICIA E INMU	HAYA DELA TORRE Y MEDINA	BUENOS AIRES				ARG	Allergy and Infectious Diseases Research	000	3	2/17/2016	NON-COMPETING CONTINUATION	$133,400
														Subtotal = $133,400

Issue Date FY: 2015 ( Subtotal = $133,400 )
2015	2015	CENTRO DE INVESTIGACIONES EN BIOQUIMICA CLINICIA E INMU	HAYA DELA TORRE Y MEDINA	BUENOS AIRES				ARG	Allergy and Infectious Diseases Research	000	2	2/19/2015	NON-COMPETING CONTINUATION	$133,400
														Subtotal = $133,400

Issue Date FY: 2014 ( Subtotal = $133,400 )
2014	2014	CENTRO DE INVESTIGACIONES EN BIOQUIMICA CLINICIA E INMU	HAYA DELA TORRE Y MEDINA	BUENOS AIRES				ARG	Allergy and Infectious Diseases Research	002	1	5/26/2014	NEW	$133,400
2014	2014	CENTRO DE INVESTIGACIONES EN BIOQUIMICA CLINICIA E INMU	HAYA DELA TORRE Y MEDINA	BUENOS AIRES				ARG	Allergy and Infectious Diseases Research	001	1	5/19/2014	NEW	-$133,400
2014	2014	CENTRO DE INVESTIGACIONES EN BIOQUIMICA CLINICIA E INMU	HAYA DELA TORRE Y MEDINA	BUENOS AIRES				ARG	Allergy and Infectious Diseases Research	000	1	2/14/2014	NEW	$133,400
														Subtotal = $133,400

Grand Total All Awards = $667,480

Top

All Categories

About

Search

Reports

Data Submission

Award Information

IL-17RA-signaling cytokines in the regulation of CD8 T cell immunity to T. cruzi

Award Number: R01AI110340

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: 03/01/2014

PERIOD OF PERFORMANCE END DATE: 02/29/2020

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer