# Dissecting the Role of DDR2 in the Modulation of Antibacterial Host Defense Post Fibrotic Lung Injury

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $37,770

## Abstract

Project Abstract
Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the progression of collagen deposition in the
lung and eventual loss of lung function. IPF is fatal and treatments for the disease are limited and lacking efficacy.
Much of the mortality associated with IPF can be attributed to acute exacerbation (AE), or a rapid deterioration
in lung function, often leading to death within a few months of diagnosis. However, studies within the last decade
have also recognized a role for bacteria within the lung in exacerbating IPF disease course. One study found
that respiratory infections were the cause of similar mortality rates in hospitalized IPF patient populations
compared to AE. Other studies have identified the presence of bacterial genera Staphylococcus and
Streptococcus within the lung as being associated with poor IPF patient outcomes. Our lab has preliminary data
indicating that mice with bleomycin-induced fibrotic lung injury that were subsequently infected with
Staphylococcus aureus or Streptococcus pneumoniae had decreased survival compared to mice with fibrotic
lung injury alone. We have also determined that fibrotic mice have impaired ability to clear a bacterial infection
compared to non-fibrotic mice. Therefore, in this proposal, we seek to identify the effect of fibrosis on the immune
response to bacterial infection. We have identified the collagen receptor discoidin domain receptor 2 (DDR2) as
a possible mediator of immune cell function following fibrotic lung injury. We have determined that DDR2 is
downregulated in macrophages isolated from fibrotic mice and that DDR2-/- bone marrow-derived macrophages
show decreased levels of bacterial phagocytosis and neutrophil chemokine production, two critical functions in
the clearance of bacterial infections. This proposal will test the hypothesis that fibrotic lung injury impairs
antibacterial host defense via the downregulation of DDR2. This hypothesis will be tested through two specific
aims: 1) determine the role of collagen receptor DDR2 in regulating macrophage antibacterial responses
following pulmonary fibrosis and 2) characterize the role of DDR2 in mediating decreased neutrophil recruitment
in post-fibrosis bacterial pneumonia. Experiments for these aims will be completed with the use of genetically
engineered mouse models, cells derived from such mice, and in vitro assays studying the role of DDR2 in various
immune cell functions. The results from these innovative studies may inform treatments that help improve IPF
patient outcomes following respiratory infection. Completion of this proposal will also allow for the applicant to
receive rigorous training in experimental design, implementation, and interpretation that will help her become a
successful, independent scientist.

## Key facts

- **NIH application ID:** 10360419
- **Project number:** 5F31HL152509-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Helen Ivory Warheit-Niemi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,770
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360419

## Citation

> US National Institutes of Health, RePORTER application 10360419, Dissecting the Role of DDR2 in the Modulation of Antibacterial Host Defense Post Fibrotic Lung Injury (5F31HL152509-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360419. Licensed CC0.

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