# Pneumonia and Alveolar Macrophage Resilience

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $45,520

## Abstract

Project Summary
Bacterial pneumonia remains a major health burden at the two ends of the age spectrum. It is
the host response to these microbes that leads to both susceptibility and pathogenesis for this
disease, emphasizing the need to better understand the host response which determines the
occurrence and severity of pneumonia. Alveolar macrophages (AM) are long-lived cells capable
of surviving infections and inflammation, but microbes can cause programmed necrosis of AM.
Countering AM death decreases pneumonia severity, suggesting that this AM response is a
lynchpin of lung defense. Dying AM are replaced by the local proliferation of yolk sac-derived
AM plus the recruitment of bone marrow-derived monocytes which differentiate into AM.
Distinctive biology of these 2 AM subsets is an important knowledge gap. Recovery from
previous respiratory infections remodels lung immunity to make pneumonia less likely, involving
several arms of adaptive and innate immunity that are beginning to be elucidated. Whether and
how AM are altered in these previously infected and now protected lungs has not been
examined. We hypothesize that recovery from previous respiratory infections remodels the pool
of AM and increases resilience against microbe-induced programmed necrosis. We have
collected preliminary data which support this central hypothesis and guide further investigation.
We will examine our central hypothesis by pursuing the following specific aims: (1) To test the
hypothesis that recovery from previous respiratory infections tilts the balance of yolk sac
progenitor- vs. bone marrow hematopoiesis-derived AM in the lung, followed by distinctive
responses of these 2 AM sub-types when those experienced lungs get infected. (2) To test the
hypothesis that IFN-γ renders alveolar macrophages more resilient. These aims will be
approached using combinations of genetically engineered mice, blocking antibodies,
recombinant cytokines, cell sorting, and RNAseq analyses. Elucidating what dictates
macrophage resilience and finding ways to interfere with pathogen-induced macrophage
programmed cell death will be steps towards new approaches for preserving macrophages to
promote lung health and prevent pneumonia, to recognizing and potentially circumventing the
natural loss of tissue resilience that accompanies aging, and to improving vaccine design to
extend beyond antibody-mediated protection.

## Key facts

- **NIH application ID:** 9921207
- **Project number:** 5F31HL147397-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Emad Arafa
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921207

## Citation

> US National Institutes of Health, RePORTER application 9921207, Pneumonia and Alveolar Macrophage Resilience (5F31HL147397-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9921207. Licensed CC0.

---

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