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Investigating the ontogeny and functions of trained macrophages in type 2 immunity

Award Number: R01AI191564
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: 02/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Investigating the ontogeny and functions of trained macrophages in type 2 immunity - ABSTRACT: Helminth parasites infect an estimated 2 billion people causing significant malnutrition, growth retardation and immunopathology. Further, these debilitating infections also exert enormous economic burdens on heavily infected areas. It is well established that type 2 responses initiate beneficial inflammation that promotes disease tolerance and parasite expulsion. However, when dysregulated, infection-induced type 2 immunity can lead to severe immunopathology including emphysema and fibrosis. Thus, it is essential that we gain a better understanding of how type 2 inflammation is properly balanced to develop better therapeutic strategies to treat these devastating infections and other forms of lung pathology. Our studies and those of others have also shown that lung macrophages play important roles in antihelminth immunity and insights into how this protective macrophage population is sustained may provide the basis for new therapeutics that target resistance and decreased worm burden. We have identified unappreciated and significant roles for infection-induced neutrophils and basophils in mediating these pathways. Specifically, we have discovered that lung neutrophils enhance infection-induced type 2 inflammation and macrophage activation while lung basophils restrict these responses. Collectively, these studies demonstrated that interactions between distinct innate immune cells in the lung are required to properly regulate macrophage responses post-helminth infection. The field of innate immune memory or trained immunity suggests that once activated, macrophages can maintain a level of non-specific memory resulting in enhanced effector functions following subsequent stimulation. While this is well established in the field of type 1 immunity, how macrophages are trained in the context of type 2 inflammation remains less defined. Our preliminary studies have shown that Nippostrongylus brasiliensis (Nb)-educated macrophages isolated 45 days post-infection confer enhanced resistance to Nb when transferred into the lungs of an otherwise naive host. We hypothesize that coordinated extracellular interactions with macrophages, including neutrophils and basophils, influence intracellular metabolic and epigenetic changes that mediate the development and persistence of the Nb- induced lung macrophages. We will now investigate how this long-lived macrophage phenotype is sustained. Aim 1 will focus on the role of extracellular factors including neutrophils and basophils and changes in lung architecture that may contribute to the formation and persistence of the long-lived antihelminth macrophage phenotype. Aim 2 will investigate intracellular changes in macrophages, directly examining metabolic and epigenetic changes occurring in macrophages that instruct the development and persistence of their training. In this context, we will directly examine whether intrinsic mechanisms are sufficient to support the trained macrophage phenotype. Collectively, these studies address an important knowledge gap and will provide mechanistic insight into the development of memory-like macrophages in the context of type 2 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: 2026 ( Subtotal = $764,590 )
2026	2026	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	000	1	2/1/2026	NEW	$764,590
														Subtotal = $764,590

Grand Total All Awards = $764,590

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Investigating the ontogeny and functions of trained macrophages in type 2 immunity

Award Number: R01AI191564

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: 02/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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