# Impact of interferon λ signaling on lung macrophage function and type 17 immunity during bacterial super-infection following influenza

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $10,560

## Abstract

Abstract
Lung diseases and syndromes caused by respiratory pathogens represent a leading cause of death worldwide.
Each year, influenza infections result in a significant number of fatalities, a majority of which are complicated by
secondary bacterial super-infection. Primary influenza infection has been shown to increase susceptibility to
secondary methicillin-resistant Staphylococcus aureus (MRSA) infection by altering the pulmonary host immune
response and damaging the lung epithelial barrier, leading to increased morbidity and mortality. Macrophages,
both lung-resident and those recruited to the lung, are important in super-infection resolution as they engulf,
degrade, and present bacterial antigen to adaptive immune cells, ultimately leading to activation of type 17 cells,
which promote pathogen clearance. While the role of interferon-(IFN)α/β during super-infection has been well
characterized, type III IFNs have not been as extensively studied within the context of the lung. Data shows that
IFNα/β are involved in type 17 attenuation after primary influenza infection, which may indicate that IFNλ exhibits
similar inhibitory functions due to overlapping signaling pathways, although the potential for unique functions on
lung cells is unresolved.
Our lab has preliminary data suggesting that administration of exogenous IFNλ during super-infection reduces
bacterial uptake by neutrophils and monocyte-derived cells, but the specific cell subsets impacted are unknown.
I hypothesize that lung-resident macrophages are sensitive to IFNλ and that IFNλ signaling impairs
phagocytosis and the type 17 immune response during super-infection. In the proposed studies, I will
determine which myeloid subsets express the IFNλ receptor (IFNLR1) and identify how intact or disrupted IFNλ
signaling broadly impacts lung injury and resolution after infection. More specifically, these experiments will
determine how IFNλ impacts MRSA uptake and the initiation of a type 17 immune response during super-
infection. IFNλ administration has been considered for therapeutic potential, and the outcomes of this proposal
will shed light on potential caveats to the use of IFNλ as a possible treatment method during super-infection.
Further, demonstration of the effects of IFNλ on myeloid cells will potentially be applicable to several other
settings where an antiviral interferon response is observed.

## Key facts

- **NIH application ID:** 10843732
- **Project number:** 5F31HL164031-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Danielle Antos
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $10,560
- **Award type:** 5
- **Project period:** 2023-05-01 → 2024-08-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843732

## Citation

> US National Institutes of Health, RePORTER application 10843732, Impact of interferon λ signaling on lung macrophage function and type 17 immunity during bacterial super-infection following influenza (5F31HL164031-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843732. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*