The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung
NHLBI - National Heart Lung and Blood Institute
About This Grant
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a significant threat to global public health. Pulmonary immunopathological damage plays a role in driving pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan failure in severe COVID-19. Therefore, dissecting the pulmonary immune response to SARS-CoV-2 infection is critical to under- stand disease pathogenesis and develop more effective therapeutics. Targeting of type 2 immune pathways is a potential avenue of therapeutic intervention in severe COVID-19. In particular, research has demonstrated a link between the type 2 cytokine IL-13 and COVID-19 severity. This proposal builds on the preliminary experi- ments demonstrating that blockade of the alarmin cytokine IL-33 confers protection in a mouse model of COVID- 19. IL-33 is a potent inducer of type 2 immunity in the lung, as its receptor ST2 is constitutively expressed by type 2 cells including type 2 innate lymphoid cells (ILC2s). It is hypothesized that IL-33/ST2 signaling induces a pathogenic inflammatory environment in the acutely infected lung by activating IL-13-secreting ILC2s and that IL-33-mediated inflammation enhances disruption of the respiratory epithelial barrier. To test this hypothesis, the impact of IL-33/ST2 signaling axis blockade on the inflammatory environment in the acutely infected lung will be described through assessment of the immune cell populations and the transcriptional profile of the respiratory epithelium (Aim 1). Considering that SARS-CoV-2-mediated ARDS is characterized by pulmonary inflammation and respiratory epithelial barrier disruption, these descriptive studies will elucidate pathways through which IL- 33 may drive pathogenesis. Further, the mechanism through which the IL-33/ST2 signaling axis drives patho- genesis will be directly tested (Aim 2). Mouse models of ILC2 depletion, selective ST2 knockout in ILC2s, and adoptive ILC2 transfer will be used to test whether IL-33-activated ILC2s drive pulmonary pathogenesis in the context of acute SARS-CoV-2 infection. Collectively, the proposed experiments will determine the mechanism underlying IL-33-mediated pathogenesis. This research is significant because it will further our understanding of how modulation of type 2 immunity can serve as a novel and promising therapeutic strategy in the treatment of respiratory viral infection-induced pulmonary pathology.
Grant Summary
The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung is a NHLBI - National Heart Lung and Blood Institute grant providing up to $39K for university, nonprofit, healthcare org. Applications are due 2028-02-28 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $39K
2028-02-28
- 1Confirm your organization is eligible for The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung from NHLBI - National Heart Lung and Blood Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NHLBI - National Heart Lung and Blood Institute before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NHLBI - National Heart Lung and Blood Institute's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung: Frequently Asked Questions
Who is eligible for the The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung?
The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung is offered by NHLBI - National Heart Lung and Blood Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung provide?
The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung provides up to $39K per award from NHLBI - National Heart Lung and Blood Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung deadline?
Applications for The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung are due 2028-02-28 (open). Because deadlines can change, verify the date with the funder, NHLBI - National Heart Lung and Blood Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung?
To apply for The Pathogenic Role of IL-33 in the SARS-CoV-2-Infected Lung, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NHLBI - National Heart Lung and Blood Institute.