Saturday, August 2, 2025 8/2/2025

Molecular Analysis of Host Immune Response in Leprosy

Award Number: R01AI022553
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: 01/01/1991
PERIOD OF PERFORMANCE END DATE: 05/31/2029

Group Awards By:

View Award Description

Molecular Analysis of Host Immune Response in Leprosy - PROJECT SUMMARY / ABSTRACT T cells are required for protection against intracellular infections such as leprosy and tuberculosis; however, the specific mechanisms by which they contribute to host immunity remain unresolved. Leprosy, caused by the intracellular pathogen Mycobacterium leprae (mLEP), provides an accessible model to investigate human immune responses to intracellular bacterial infection. The spectrum of clinical manifestations of leprosy correlates with the immune response to mLEP. Patients with tuberculoid leprosy (T-lep) develop protective immunity and eliminate the infection, whereas those with lepromatous leprosy (L-lep) sustain a progressive infection. The dynamics of T cell immunity can be studied in the context of the reversal reaction (RR), in which patients upgrade from L-lep to T-lep. We established that in patients with leprosy, T cell subsets differ dramatically between the blood and lesions, indicating the importance of studying the immune response at the site of disease. During the first 38 years of this R01, we discovered new mechanisms by which CD4+ and CD8+ T cells engender antimicrobial activity against mLEP in infected human macrophages (MØs), which we also showed to be relevant in Mycobacterium tuberculosis infection. These include 1) cytolytic T lymphocyte release of the antimicrobial protein granulysin; 2) Th1 cell secretion of IFN- which activates vitamin D-dependent induction of the antimicrobial proteins cathelicidin and DEFB4 in MØs; and 3) Th17 cell release of the antimicrobial protein IL-26, which enters myeloid cells targeting intracellular bacteria. None of these mechanisms exist in mice, necessitating the study of human disease. By integrating scRNA-seq and spatial transcriptomics, we identified an ecosystem of T cells, MØs, keratinocytes, fibroblasts, and endothelial cells that together express 66 genes involved in the antimicrobial response in leprosy. We also discovered that TREM2 MØs are a major MØ subpopulation in the disseminated L-lep form of leprosy, representing the mLEP- infected foamy MØs that are unable to eliminate the pathogen. We hypothesize that T cell-dependent antimicrobial mechanisms can overcome immune suppression in TREM2 MØs and thus eliminate mLEP. Our specific aims are to: Aim 1: Elucidate the mechanisms by which T cells mediate an antimicrobial response to intracellular mycobacteria, Aim 2: Define mechanisms by which TREM2 MØs contribute to the pathogenesis of progressive infection in leprosy; and, Aim 3: Identify immune pathways that can augment antimicrobial responses in leprosy, including in CD8+ T cells and TREM2 MØs. The proposed studies will provide insights into the mechanisms of pathogenesis and host defense in intracellular bacterial infections.


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 = $789,331 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	41	5/19/2025	NON-COMPETING CONTINUATION	$789,331
2025	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	39	2/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $789,331

Issue Date FY: 2024 ( Subtotal = $803,706 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	40	9/4/2024	COMPETING CONTINUATION	$78,932
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	40	4/26/2024	COMPETING CONTINUATION	$724,774
														Subtotal = $803,706

Issue Date FY: 2023 ( Subtotal = $666,666 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	39	6/30/2023	NON-COMPETING CONTINUATION	$666,666
														Subtotal = $666,666

Issue Date FY: 2022 ( Subtotal = $666,666 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	38	6/28/2022	NON-COMPETING CONTINUATION	$666,666
														Subtotal = $666,666

Issue Date FY: 2021 ( Subtotal = $666,666 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	37	6/24/2021	NON-COMPETING CONTINUATION	$666,666
														Subtotal = $666,666

Issue Date FY: 2020 ( Subtotal = $666,666 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	36	6/15/2020	NON-COMPETING CONTINUATION	$666,666
2020	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	34	2/4/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $666,666

Issue Date FY: 2019 ( Subtotal = $680,666 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	35	4/9/2019	COMPETING CONTINUATION	$680,666
														Subtotal = $680,666

Issue Date FY: 2018 ( Subtotal = $556,923 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	34	5/25/2018	NON-COMPETING CONTINUATION	$556,923
														Subtotal = $556,923

Issue Date FY: 2017 ( Subtotal = $556,923 )
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	33	7/11/2017	NON-COMPETING CONTINUATION	$556,923
														Subtotal = $556,923

Issue Date FY: 2016 ( Subtotal = $556,923 )
2016	2016	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	32	6/8/2016	NON-COMPETING CONTINUATION	$556,923
														Subtotal = $556,923

Issue Date FY: 2015 ( Subtotal = $693,983 )
2015	2015	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	30	3/5/2015	SUPPLEMENT FOR EXPANSION	$68,530
2015	2015	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	31	6/22/2015	NON-COMPETING CONTINUATION	$625,453
														Subtotal = $693,983

Issue Date FY: 2014 ( Subtotal = $572,327 )
2014	2014	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	30	6/25/2014	COMPETING CONTINUATION	$572,327
2014	2013	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	29	6/18/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $572,327

Issue Date FY: 2013 ( Subtotal = $566,339 )
2013	2013	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	29	12/1/2012	NON-COMPETING CONTINUATION	$542,243
2013	2013	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	29	8/9/2013	NON-COMPETING CONTINUATION	$24,096
														Subtotal = $566,339

Issue Date FY: 2012 ( Subtotal = $659,484 )
2012	2012	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	002	28	2/14/2012	SUPPLEMENT FOR EXPANSION	$71,240
2012	2012	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	28	11/30/2011	NON-COMPETING CONTINUATION	$540,226
2012	2012	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	003	28	6/14/2012	NON-COMPETING CONTINUATION	$48,018
2012	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	001	26	12/16/2011	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $659,484

Issue Date FY: 2011 ( Subtotal = $590,511 )
2011	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	27	6/21/2011	NON-COMPETING CONTINUATION	$40,418
2011	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	27	11/26/2010	NON-COMPETING CONTINUATION	$550,093
														Subtotal = $590,511

Issue Date FY: 2010 ( Subtotal = $674,825 )
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	002	26	9/7/2010	SUPPLEMENT FOR EXPANSION	$78,364
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	26	5/25/2010	NON-COMPETING CONTINUATION	$54,224
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	26	12/3/2009	NON-COMPETING CONTINUATION	$542,237
														Subtotal = $674,825

Issue Date FY: 2009 ( Subtotal = $601,513 )
2009	2009	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	25	12/9/2008	COMPETING CONTINUATION	$601,513
2009	2008	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	24	12/9/2008	NON-COMPETING CONTINUATION	$0
														Subtotal = $601,513

Issue Date FY: 2008 ( Subtotal = $482,972 )
2008	2008	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	24	2/27/2008	NON-COMPETING CONTINUATION	$482,972
														Subtotal = $482,972

Issue Date FY: 2007 ( Subtotal = $484,806 ) (Continued on the next page)
Grand Total All Awards = $15,519,677

Page 1 of 2 (69 items)12

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Analysis of Host Immune Response in Leprosy

Award Number: R01AI022553

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: 01/01/1991

PERIOD OF PERFORMANCE END DATE: 05/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer