Investigating the protective role of type III interferon signaling in the neonatal response to influenza virus infection
Ended Project Grant Awarded Last action
- Award ID
- F31AI191792
- Recipient
-
Drexel University UEI XF3XM9642N96
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $43,641
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Place of performance
- Philadelphia, PA 19102, USA
Award details come from USAspending.gov.
Description
- Abstract
- Immunological and developmental deficiencies are major contributors to influenza virus (IAV) susceptibility in infants, with increased reliance on the innate immune system to respond to pathogens. Type I (IFN-I) and III (IFN-III) interferons are key components of this innate immune response. In adults, interferons control viral replication; however, the protective or pathogenic role of interferon signaling in the neonate is not well understood. Using our innovative neonatal murine model of IAV infection, ablation of IFN-I signaling in neonates significantly improved survival, while removal of IFN-III signaling exacerbated pathogenesis and all neonates succumbed to infection. Therefore, there is a contrasting role of these two IFN in the developing neonate. In adults, IFN-I and IFN-III have been reported to disrupt lung repair following respiratory viral infection. Recently, we have shown that IFN-I signaling in neonatal type II epithelial cells disrupts cell repair early during IAV infection and reduces pulmonary tight junction integrity during peak mortality. However, the relative role type III interferons play in these responses is a GAP in knowledge. Here, we hypothesize that in IAV-infected murine neonates, type III interferon signaling supports tight junction integrity and essential epithelial cell repair, thus reducing pathogenic lung damage. While addressing this hypothesis, I will build upon my base skillset of immunology and molecular biology techniques under the mentorship of alison carey, MD, a neonatologist and expert in neonatal immunology. Joshua chang mell, PHD, a long-standing collaborator of the carey lab, will guide me to expand my bioinformatics skillset by learning unix and R for analysis of single cell RNA-sequencing data. First, we will determine how IFN-III impacts tight junction integrity in the lungs of infected WT, IFNLR1-/- and ifnar-/- neonates, which lack IFN-I signaling, via immunohistochemistry and an in vivo barrier function test. Concurrently, we will assess immune cell recruitment and cytokine production through flow cytometry and luminex analysis. Furthermore, we aim to evaluate the therapeutic potential of IFN-III supplementation by treating WT neonates following IAV infection. Second, single cell sequencing will be employed to assess the impact of IFN-III on transcriptional signatures within key epithelial cell populations. Here, I will utilize unix language for data processing and R-based seurat for data analysis. Differentially expressed genes related to anti-viral and cell repair pathways will be determined in pulmonary non-immune cells including type II and type I alveolar epithelial cells, fibroblasts, and endothelial cells between IAV-infected WT, IFNLR1-/-, and ifnar-/- neonates. Findings from this proposal will provide insight into the age specific role of IFN-III in the setting of neonatal viral infections and inform the development of targeted therapeutics for this at- risk population. Importantly, I will gain a unique skillset, which combines molecular immunology work in an age- appropriate in vivo model with high-level bioinformatics analysis. This skillset is critical to bridge the GAP between immunologists and bioinformaticians to develop therapeutics in the industry research setting.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$43,641 | |
| Amendment | $43,641 | |
| Original award | $43,641 |
Quick answers
Who received award F31AI191792?
F31AI191792 was awarded to Drexel University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on October 5, 2026.
How much is award F31AI191792 worth?
$43,641 has been obligated on F31AI191792.
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