# Modulation of Viral Antigen Presentation in the Lung

> **NIH NIH U19** · JACKSON LABORATORY · 2022 · $445,279

## Abstract

PROJECT SUMMARY RESEARCH PROJECT 1
Project 1 will elucidate how the networks of antigen presenting cells (APCs) in the human lung regulate immunity
to respiratory viruses. The goal is to also explain how microbiome-driven lung inflammation or inflammation that
is linked with neoplastic processes affects such responses. Project 1 is founded on the scientific premise that
identifying the pathways underpinning immune cell responses to respiratory viruses in situ is key to identifying
targets and strategies for designing and developing improved vaccines. Our overall hypothesis is that the lung
environment defines immunological status, i.e., the “immune set-point”, and the function of tissue-resident
dendritic cells (DCs). We further posit that the immune set-point impacts the fate of antigen and the quality and
magnitude of ensuing mucosal T-cell immunity. Implicit in this hypothesis is a role for the local microbiome, which
we predict contributes to the immediate environment by direct and indirect crosstalk with immune cells and
ensuing inflammatory responses. We propose three aims: Aim 1 will test the hypothesis that steady state cellular
and molecular networks in human lung tissue regulate the early response to respiratory viruses. We will define
the composition and functional status of human lung tissue across a range of clinical situations: normal lung,
uninvolved cancer patient lung and cancer-involved lung tissue. Correlative analyses with upstream
environmental regulators such as the microbiome will identify pathways that control the magnitude and quality
of ensuing adaptive immunity. Aim 2 will test the hypothesis that the generation of anti-viral T-cell immunity is
modulated by lung epithelial cell (EC)-DC crosstalk and that this crosstalk is further modulated by commensal
bacteria. We will determine how lung DCs exposed to virally-infected lung alveolar epithelial cells (AECs)
modulate the differentiation of T cells; we will establish the molecular programs in DCs triggered by lung ECs
that can explain T-cell phenotypes; and we will determine how the bacteria cultured from the mouth and upper
respiratory tract impacts lung ECs and downstream responses. Aim 3 will test the hypothesis that the lung
microenvironment modulates the cross-presentation capacity of lung-resident APCs thereby dictating the fate of
viral antigen-specific CD8+ T cells. We will assess viral distribution and cross-presentation in the context of
resistant and susceptible cells defined by expression of a viral resistance gene, Rab15; and the access of
opsonized virus to cross-presenting compartments in lung myeloid cells. Thus, this project will elucidate the key
innate immune networks that determine the overall outcome of adaptive immune responses during respiratory
viral infections. Along with other Projects, our proposed research has a high potential to discover novel target
molecules that will eventually help us design improved therapeutics and vaccines for respirato...

## Key facts

- **NIH application ID:** 10371235
- **Project number:** 5U19AI142733-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Anna Karolina Palucka
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $445,279
- **Award type:** 5
- **Project period:** 2019-03-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371235

## Citation

> US National Institutes of Health, RePORTER application 10371235, Modulation of Viral Antigen Presentation in the Lung (5U19AI142733-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371235. Licensed CC0.

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