Saturday, July 5, 2025 7/5/2025

Protective and pathologic functions of macrophages induced by helminths

Award Number: R01AI131634
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: 12/20/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2022

Group Awards By:

View Award Description

Protective and pathologic functions of macrophages induced by helminths - ABSTRACT The global prevalence of soil transmitted helminth infections is estimated at two billion individuals infected, with an estimated 870 million children at risk of becoming infected. Helminth infections can lead to significant malnutrition, growth retardation, severe immunopathology, and exert enormous economic burdens on local communities. Helminth parasites take complex migratory cycles through multiple tissues before entering the intestine of their host. To combat these challenges, the mammalian immune system has evolved mechanisms to maintain a delicate balance between promoting beneficial inflammation needed to reduce parasitic burdens and limiting pathologic inflammation to maintain tissue integrity. The importance of maintaining this balance is evident by the severe pathology that presents in patients exhibiting dysregulated immune responses to helminths. Despite the importance of balancing protective and pathologic responses in the context of helminth infections, the cellular and molecular events that regulate these pathways remain unknown. It is well established that T helper type 2 (TH2) cytokine responses, characteristics of helminth-induced immunity in humans and mice, are required to both promote worm clearance and limit infection-induced tissue damage. An emerging body of literature has now shown that type 2 cytokine-activated macrophages operate as critical regulators of these distinct pathways. In addition, our recent work has also demonstrated that interactions between neutrophils and lung macrophages are required for macrophages to acquire anti-Nippostrongylus brasiliensis (Nb) effector functions in the airways. Moreover, our preliminary data suggest that interactions with basophil populations are required for macrophages to initiate wound healing responses in the lung. Collectively these studies provide the hypothesis that coordinated interactions with Nb-primed innate immune cell populations are necessary for macrophages to acquire host-protective effector functions. This will be directly tested in Aim 1 of this proposal focused on interrogating the accessory cells necessary to promote macrophage activation in the lung following Nb infection. It is well established that long-lived tissue-derived macrophages (TD-Macs) populate the lungs during fetal development, while monocyte-derived macrophages (Mo-Macs) accumulate in tissue environments in the context of ongoing inflammation. Further, it has been demonstrated that TD-Macs and Mo-Macs can exhibit distinct phenotypes in the context of helminth infections. Despite these advances the distinct contributions of TD-Macs and Mo-Macs to anti-helminth immunity and tissue integrity remain unknown. This will be directly tested in Aim 2 of this proposal focused on elucidating the distinct and common effector functions of lung macrophage populations following Nb infection. These aims will be addressed employing the collective intellectual and scientific resources of the Siracusa and Gause laboratories and the results of these studies will increase our understanding of how pulmonary macrophages are programed in the context of acute inflammation.


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: 2024 ( Subtotal = $0 )
2024	2022	RUTGERS, THE STATE UNIVERSITY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	5	10/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $495,400 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	5	11/19/2021	NON-COMPETING CONTINUATION	$495,400
														Subtotal = $495,400

Issue Date FY: 2021 ( Subtotal = $507,883 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	4	12/4/2020	NON-COMPETING CONTINUATION	$507,883
														Subtotal = $507,883

Issue Date FY: 2020 ( Subtotal = $560,717 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	3	11/26/2019	NON-COMPETING CONTINUATION	$560,717
														Subtotal = $560,717

Issue Date FY: 2019 ( Subtotal = $519,201 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	2	11/13/2018	NON-COMPETING CONTINUATION	$495,400
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	001	2	8/23/2019	SUPPLEMENT FOR EXPANSION	$23,801
														Subtotal = $519,201

Issue Date FY: 2018 ( Subtotal = $495,400 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Allergy and Infectious Diseases Research	000	1	12/20/2017	NEW	$495,400
														Subtotal = $495,400

Grand Total All Awards = $2,578,601

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Protective and pathologic functions of macrophages induced by helminths

Award Number: R01AI131634

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: 12/20/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer