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Characterizing NLRP11 Activation by Mycobacteria to Enhance Innate Immune Responses

Award Number: R21AI196587
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: 02/02/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Characterizing NLRP11 Activation by Mycobacteria to Enhance Innate Immune Responses - The NLRP11 protein is only expressed in primates and participates in the activation of the canonical NLRP3 and non-canonical caspase-4 inflammasome activation after infection with gram-negative bacteria. We found that the atypical gram-positive pathogen Mycobacterium tuberculosis (Mtb) and the opportunistic pathogen M. kansasii both activate the non-canonical NLRP11 inflammasome in a caspase-4/5-dependent pathway. In specific aim 1.1 we propose to screen a collection of mycobacterial species, including Mtb strains of the major documented lineages, to characterize which ones are being recognized by the NLRP11/caspase-4 inflammasome. In specific aim 1.2 we will screen subcellular fractions of Mtb to identify which one contains the ligand(s) being detected by NLRP11 and/or caspase-4. Finally, in specific aim 2 we propose a genetic gain-of-function screen to discover the genes in Mtb that encode for the putative ligand(s). The discovery of a novel ligand originating from the atypical gram-positive Mtb will of great significance for structure-function analysis of the NLRP11/caspase-4 inflammasome. Also, the knowledge could potentially be exploited to overexpress the ligand in the current tuberculosis vaccine strain to improve its immunogenicity.


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: 2026 ( Subtotal = $421,720 )
2026	2026	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	2/2/2026	NEW	$421,720
														Subtotal = $421,720

Grand Total All Awards = $421,720

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Characterizing NLRP11 Activation by Mycobacteria to Enhance Innate Immune Responses

Award Number: R21AI196587

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: 02/02/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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