# Effector-triggered immunity against Legionella pneumophila in dendritic cells

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $200,000

## Abstract

Project Summary
Intracellular bacterial pathogens such as Legionella pneumophila, the causative agent of the severe pneumonia
Legionnaires' disease, are responsible for significant disease burden in the United States every year. The
growing use of immunosuppressive drugs, particularly TNF blockrs, to treat autoimmune diseases comes with a
significantly increased risk of infection by intracellular bacterial pathogens, including Mycobacterium tuberculosis
and Legionella pneumophila. The increasing numbers of individuals who are functionally immunocompromised
due to growing use of TNF blockade, combined with the growing spread of antibiotic resistance, poses a serious
public health concern. Our goal is to define the mechanisms by which TNF promotes immune defense against
Legionella pneumophila. This information may enable development of targeted therapeutics that promote anti-
bacterial defense in immunocompromised individuals. Critically, in new preliminary studies that take advantage
of our ability to dissect the interactions between Legionella and dendritic cells, we find that TNF signaling drives
a Legionella effector-triggered immune response that induces apoptosis in dendritic cells, thereby restricting
intracellular Legionella replication. The proposed studies will provide fundamental insight into how TNF-mediated
effector-triggered immunity promotes control of intracellular Legionella replication within dendritic cells. This
information may provide a basis for the development of improved therapeutics for the treatment of Legionella
and other bacterial pathogens.

## Key facts

- **NIH application ID:** 10881952
- **Project number:** 5R21AI172178-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Sunny Shin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,000
- **Award type:** 5
- **Project period:** 2023-07-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881952

## Citation

> US National Institutes of Health, RePORTER application 10881952, Effector-triggered immunity against Legionella pneumophila in dendritic cells (5R21AI172178-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10881952. Licensed CC0.

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