# Role of the Trophic Forms of Pneumocystis in Lung Response to Infection

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $188,070

## Abstract

Pneumocystis (PC) pneumonia continues to be a leading cause of opportunistic infections in
patients living with HIV. Though we are thirty years into the HIV epidemic very little is known
about the lifestyle of the PC organism and how it interacts with the immune system. The field is
hampered by the inability to culture the organisms for more than a couple weeks and the
problem of separating the two identifiable life forms, the ascus and trophic forms, resulting in a
paucity of information regarding how these separate life forms interact with the host and the
immune response. Recently β-glucan synthesis inhibitors (a class of drugs called
echinocandins) have been used to eliminate the ascus form of the organisms in vivo giving us
the ability to obtain a purified population of trophic forms and to examine trophic form
interactions with host immune cells. Our preliminary data demonstrates that trophic forms of PC
inhibit TNF production of alveolar macrophages after stimulation by lipopolysaccharide (LPS), β-
glucans, or lipoteichoic acid (LTA) in vitro. Additionally, in vivo we found that trophic forms
inhibit TNF production in the lungs of mice challenged with a small dose of LPS. We
hypothesize that the trophic forms of PC act to temper the inflammatory response to β-glucans
in the ascus forms of PC. The goal of this proposal is to determine the significance and
mechanism of the inhibitory activity of trophic forms of PC. We propose two aims to address
our hypothesis. In aim 1 we will determine whether trophic forms of PC alter the balance of
inflammation induced by β-glucan in vivo. In aim 2 we will determine whether trophic forms of
PC dampen inflammation induced by innate immune responses and identify pattern recognition
receptors on macrophages that interact with tropic forms of PC.

## Key facts

- **NIH application ID:** 9957015
- **Project number:** 5R21AI146016-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Beth A Garvy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,070
- **Award type:** 5
- **Project period:** 2019-06-17 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957015

## Citation

> US National Institutes of Health, RePORTER application 9957015, Role of the Trophic Forms of Pneumocystis in Lung Response to Infection (5R21AI146016-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957015. Licensed CC0.

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