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Investigating the requirement of the commensal microbiota for long term T cell immunity

Award Number: R21AI151987
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: 03/24/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Investigating the requirement of the commensal microbiota for long term T cell immunity - PROJECT SUMMARY The commensal microbiota inhabiting the gastrointestinal tract and other mammalian mucosal surfaces. plays fundamental roles on the induction, training and function of the host immune system, but the exact mechanisms that regulate these interactions are not fully understood. Understanding these mechanisms is a crucial step towards designing new therapeutic approaches to correct immune dysfunction caused by dysbiosis and potentially other conditions. Our initial studies show that alterations of the intestinal microbiota induced by oral administration of antibiotics selectively disrupt long-term maintenance of antigen-specific memory CD4+T cells primed in untreated mice, and impairs secondary responses to infection. In addition, we found that treatment of mice with antibiotics is associated with reduced expression of the cytokine IL- 15, which is required for maintenance of memory T cells. Together, these results led us to hypothesize that the commensall microbiota regulates memory T cell responses by stimulating the expression of factors that promotes differentiation and/ or maintenance of antigen-specific memory T cells. In this application, we will test this hypothesis. The specific aims proposed are 1) Identify mechanisms underlying the requirement of the intestinal microbiota for T cell memory and 2) Determine if antibiotic treatment alters memory T cell responses in human subjects. We anticipate that these studies will shed light on the mechanisms underlying the crosstalk between the commensal microbiota and the immune system and may inform the design of new and improved vaccine strategies


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: 2023 ( Subtotal = $3,884 )
2023	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	5/11/2023	NON-COMPETING CONTINUATION	$3,884
														Subtotal = $3,884

Issue Date FY: 2022 ( Subtotal = -$14,969 )
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	9/27/2022	NON-COMPETING CONTINUATION	-$14,969
														Subtotal = -$14,969

Issue Date FY: 2021 ( Subtotal = $250,500 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	2/4/2021	NON-COMPETING CONTINUATION	$250,500
														Subtotal = $250,500

Issue Date FY: 2020 ( Subtotal = $208,750 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	3/24/2020	NEW	$208,750
														Subtotal = $208,750

Grand Total All Awards = $448,165

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Investigating the requirement of the commensal microbiota for long term T cell immunity

Award Number: R21AI151987

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: 03/24/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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