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Regulation of CD4+ T cells in Cryptosporidium infection

Award Number: F30AI169744
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Regulation of CD4+ T cells in Cryptosporidium infection - Project Summary The apicomplexan parasite Cryptosporidium is a leading cause of diarrhea and death in immunocompromised individuals and malnourished children globally. Control of Cryptosporidium requires CD4+ T cells and the cytokine interferon-γ (IFN-γ), however there are signiﬁcant gaps in our understanding of the regulation of T cell responses against the parasite. This is in large part due to diﬃculties analyzing T cell populations in the gut. By engineering Cryptosporidium to express MHCII-restricted model antigens, I can identify parasite-speciﬁc CD4+ T cells within the gut. Using this system, I have found that CD4+ T cell responses require type 1 conventional dendritic cells (cDC1s) despite their better-studied role in CD8+ rather than CD4+ T cell responses. In addition, I have found evidence for a Th17 response elicited by infection, pointing to an IFN-γ- independent but T cell-dependent mechanism of control of the parasite that has remained elusive. I will utilize a combination of novel transgenic parasites, genetic mouse models, single-cell RNA sequencing, and high- dimensional ﬂow cytometry to test which cDC subset(s) are required for CD4+ T cell responses to Cryptosporidium (SA1), and to investigate the IFN-γ-independent, CD4+ T cell-dependent mechanism(s) of control with a focus on Th17 responses (SA2). These studies will provide an opportunity to train in cross- disciplinary approaches in parasitology and immunology to better understand how immunity to infection in the gut is regulated. The studies proposed here will impact our fundamental understanding of mucosal immunology and drive treatment and prevention for an important source of childhood mortality.


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 = -$5,455 )
2025	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	7/25/2025	NON-COMPETING CONTINUATION	-$5,455
														Subtotal = -$5,455

Issue Date FY: 2024 ( Subtotal = $29,474 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	2	5/6/2024	NON-COMPETING CONTINUATION	$1,010
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	11/3/2023	NON-COMPETING CONTINUATION	$28,464
														Subtotal = $29,474

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	10/28/2022	NEW	$51,752
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	003	1	2/14/2023	NEW	$942
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	002	1	12/5/2022	NEW	$0
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	1	10/28/2022	NEW	$0
														Subtotal = $52,694

Grand Total All Awards = $76,713

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Regulation of CD4+ T cells in Cryptosporidium infection

Award Number: F30AI169744

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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