# Protective and pathologic functions of macrophages induced by helminths

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2022 · $495,400

## Abstract

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 an...

## Key facts

- **NIH application ID:** 10312027
- **Project number:** 5R01AI131634-05
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** William Clark Gause
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,400
- **Award type:** 5
- **Project period:** 2017-12-20 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312027

## Citation

> US National Institutes of Health, RePORTER application 10312027, Protective and pathologic functions of macrophages induced by helminths (5R01AI131634-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10312027. Licensed CC0.

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