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New insights into early T cell protection during acute toxoplasmosis

Award Number: R21AI170657
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: 06/02/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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New insights into early T cell protection during acute toxoplasmosis - Project Summary/Abstract Toxoplasma gondii is an opportunistic protozoan pathogen widespread in humans, domestic animals, livestock and wildlife. The parasite is known for its ability to trigger a strong inflammatory immune response that is effective in protecting the host from infection, but that can nonetheless sometimes cause severe immune-mediated tissue damage. The long-term objective of this proposal is to understand the basis of innate and acquired immune responses that protect against infection with T. gondii and other microbial pathogens. Our preliminary data in mouse models of infection reveal aspects of early T cell immunity to Toxoplasma that have not previously been recognized, despite many decades of past research. Infection with cps1-1, a normally replication-defective Toxoplasma strain, elicits an early protective CD4+ and CD8+ T cell response that requires neither IL-12 nor Toll-like receptor adaptor MyD88, that only partially involves IFN-g, and that is essential to prevent this parasite strain from behaving in a virulent manner. The goal of the project is to understand the function of these T cells in protection against Toxoplasma. The central hypothesis driving the research is that the T cells elicited by infection display novel mechanisms of activation and anti- microbial function. Three specific aims will evaluate the hypothesis. Aim 1: Determine whether cps1-1- induced T lymphocytes function in a conventional or nonconventional antigen-specific, MHC-restricted manner. We will employ adoptive transfer approaches to determine if parasite-induced T cells act in a classical MHC class I and MHC class II restricted manner involving cognate antigen. Aim 2: Determine the transcriptomic profile and activation phenotype of cps1-1-induced CD4+ and CD8+ T lymphocytes. RNA-seq will be used to identify the underlying properties displayed by the cells necessary for protection. Aim 3: Identify effector mechanisms controlling cps1-1 infection. We will determine how two T cell mediators, CD154 and perforin, act with IFN-g to control infection employing an adoptive transfer approach along with gene knockout mice. The importance of this research is that we stand to reveal previously unrecognized aspects of immunity to Toxoplasma. This can be expected to impact our understanding and ultimately ability to treat infection with Toxoplasma and other microbial pathogens.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	2	9/26/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $186,621 )
2023	2023	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	2	5/9/2023	NON-COMPETING CONTINUATION	$186,621
														Subtotal = $186,621

Issue Date FY: 2022 ( Subtotal = $224,807 )
2022	2022	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	1	6/2/2022	NEW	$224,807
														Subtotal = $224,807

Grand Total All Awards = $411,428

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New insights into early T cell protection during acute toxoplasmosis

Award Number: R21AI170657

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: 06/02/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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