Wednesday, December 4, 2024 12/4/2024

Host and parasite determinants of Leishmania Viannia persistence in naturally infected human populations

Award Number: R01AI172887
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Project Summary The natural history of human dermal leishmaniasis caused by Leishmania Viannia species provides unequivocal evidence of long-term persistence of parasites in asymptomatically as well as symptomatically infected individuals. Persistent infection can remain asymptomatic, or can be clinically manifested through the development of mucosal or cutaneous leishmaniasis (ML and CL) following either asymptomatic infections, or as recurrent disease long after resolution of primary lesions. Molecular evidence of persistent parasites in the conjunctiva, nasal and oropharyngeal mucosal tissues, skin and blood monocytes has been documented in as many as 40% of infected individuals in endemic areas of L. Viannia transmission, however, the role of the host immune response and parasite subpopulations in promoting and sustaining Leishmania persistence in humans remains unknown. It is also well established that immune tolerance is an underlying factor of latent infection and tissue protection in infections by other protozoa such as Plasmodium and Toxoplasma. Similar host mechanisms of immune tolerance likely contribute to Leishmania persistence in the absence of signs and symptoms, since disruption of the immune homeostasis by immunosuppression or local trauma have been identified as contributing factors in recurrent CL. We hypothesize that Leishmania-host interactions eliciting strong, yet regulated innate immune responses drive the establishment of local environments of immune tolerance (metabolic and immunological), that favor Leishmania persistence in humans. In this project we will characterize the transcriptomes, metabolomes and immunophenotypes of host tissues and cells associated with persistent infection. We will genotype the corresponding Leishmania populations, and will assess the participation of immunological tolerance in human tissues where Leishmania persistence has been detected: nasal mucosa, skin and monocytes. More specifically, we will 1) Identify the molecular signature of Leishmania persistence in a cohort of patients with prior history of CL, 2) Characterize the genotype and phenotype of persister Leishmania sub-populations as they modulate human host cells, and 3) Expand an ex vivo 3D cell culture system to model the metabolic and immunological microenvironment of Leishmania persistence. This project will provide critical knowledge on the metabolic and immunological microenvironments of human tissues permissive for Leishmania persistence, define the signatures and biomarkers of persistence, and advance ex vivo models of persistent Leishmania infection.


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 = $595,744 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	11/27/2024	NON-COMPETING CONTINUATION	$595,744
														Subtotal = $595,744

Issue Date FY: 2024 ( Subtotal = $615,131 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	2	5/14/2024	NON-COMPETING CONTINUATION	$61,513
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	2	11/14/2023	NON-COMPETING CONTINUATION	$553,618
														Subtotal = $615,131

Issue Date FY: 2023 ( Subtotal = $622,462 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	1	9/19/2023	NEW	$123,821
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	12/28/2022	NEW	$498,641
														Subtotal = $622,462

Grand Total All Awards = $1,833,337

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Host and parasite determinants of Leishmania Viannia persistence in naturally infected human populations

Award Number: R01AI172887

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer