Tuesday, July 1, 2025 7/1/2025

Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis

Award Number: R01AI111914
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: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis - PROJECT SUMMARY/ABSTRACT Approximately one-fourth of the world's population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb) and those infected have a 10% lifetime risk of developing clinical pulmonary TB (PTB) disease over their lifetime. Global efforts to combat TB are hampered by the emergence of extensively drug-resistant and multidrug- resistant strains and the variable efficacy of the currently available vaccine, M. bovis Bacille Calmette Guerin. Unfortunately, the immune mechanisms that govern progression from LTBI to PTB are poorly defined, preventing rational design of treatments or vaccines that stimulate immune control of TB. Thus, there is an urgent need to better understand the immune parameters that contribute to Mtb control. The tubercle granuloma is a hallmark of TB and is important for the immune control of Mtb infection. However, not all granulomas effectively control TB, as they are seen both during LTBI and during TB reactivation (TB-R) and PTB. During the previous R01 funding period, we used human TB samples and non-human primate (NHP) and mouse models of TB to demonstrate an unequivocal protective role for inducible bronchus-associated lymphoid tissue (iBALT) containing clearly defined B-cell follicles during both primary and vaccine-induced responses to Mtb infection. Additionally, we determined that a dominant feature of granulomas during PTB is the accumulation of neutrophils that produce proinflammatory molecules such as S100A8/A9 proteins and limit iBALT formation. Our long-term goal is to develop clinical strategies to restrain Mtb growth and prevent progression from LTBI to TB disease. Based on work from this funded R01, the objective of this R01 renewal is to identify the roles of granuloma- associated B cells and neutrophils in TB infection and disease progression and to determine if iBALT is an effective target for preventing TB progression. Towards this overall goal, we propose to use both small animal and large animal models to address the following specific aims: In Specific Aim 1 we will investigate the role of iBALT-residing B cells in protecting against TB; In Specific Aim 2, we will evaluate the role of neutrophilic proteins such as S100A8/A9 in limiting iBALT during PTB, and to determine if targeting S100A8/A9 pathways will reduce TB disease and improve Mtb control; Finally, in Specific Aim 3, we will determine if iBALT structures can be targeted to prevent TB progression in Mtb-infected hosts. The knowledge to be gained from these studies is significant, as it will directly advance the development of new therapeutics and vaccine strategies for limiting TB-R and progression to TB.


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 = $1,368,144 )
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	10	6/25/2025	NON-COMPETING CONTINUATION	$1,368,144
														Subtotal = $1,368,144

Issue Date FY: 2024 ( Subtotal = $1,368,144 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	004	9	5/23/2024	NON-COMPETING CONTINUATION	$136,814
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	9	1/12/2024	NON-COMPETING CONTINUATION	$1,231,330
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	003	8	3/6/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,586,363
2024	2022	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	7	3/6/2024	NON-COMPETING CONTINUATION	-$1,363,070
2024	2021	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	6	3/6/2024	COMPETING CONTINUATION	-$223,293
														Subtotal = $1,368,144

Issue Date FY: 2023 ( Subtotal = $1,415,724 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	8	7/25/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,415,724
2023	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	7	7/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,415,724

Issue Date FY: 2022 ( Subtotal = $1,363,070 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	7	1/25/2022	NON-COMPETING CONTINUATION	$1,363,070
2022	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	6	1/27/2022	COMPETING CONTINUATION	-$613
2022	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	003	6	1/31/2022	COMPETING CONTINUATION	$0
2022	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	5	1/27/2022	NON-COMPETING CONTINUATION	$613
														Subtotal = $1,363,070

Issue Date FY: 2021 ( Subtotal = $1,391,820 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	003	6	9/28/2021	COMPETING CONTINUATION	$75,432
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	6	2/15/2021	COMPETING CONTINUATION	$1,391,820
2021	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	5	2/5/2021	NON-COMPETING CONTINUATION	$0
2021	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	5	9/28/2021	NON-COMPETING CONTINUATION	-$75,432
														Subtotal = $1,391,820

Issue Date FY: 2019 ( Subtotal = $800,095 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	5	3/15/2019	NON-COMPETING CONTINUATION	$800,095
2019	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	4	1/16/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $800,095

Issue Date FY: 2018 ( Subtotal = $800,058 )
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	4	3/26/2018	NON-COMPETING CONTINUATION	$800,058
														Subtotal = $800,058

Issue Date FY: 2017 ( Subtotal = $877,406 )
2017	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	3	3/17/2017	NON-COMPETING CONTINUATION	$877,406
														Subtotal = $877,406

Issue Date FY: 2016 ( Subtotal = $910,617 )
2016	2016	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	1/27/2016	SUPPLEMENT FOR EXPANSION	$15,462
2016	2016	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	2	3/29/2016	NON-COMPETING CONTINUATION	$895,155
														Subtotal = $910,617

Issue Date FY: 2015 ( Subtotal = $826,347 )
2015	2015	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	1	9/3/2015	NEW	$0
2015	2015	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	3/18/2015	NEW	$826,347
														Subtotal = $826,347

Grand Total All Awards = $11,121,425

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Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis

Award Number: R01AI111914

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: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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