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Updated: Sep 22, 2025

Prostaglandin Extraction and Analysis in Caenorhabditis elegans
Published on: June 25, 2013
PPAR-gamma Fun(gi) With Prostaglandin
Robert J Evans1, Simon A Johnston2
1The Francis Crick Institute, London, UK.
Abstract:
In our recent publication, we show for the first time that the fungal pathogen Cryptococcus neoformans is able to manipulate host cells by producing eicosanoids that mimic those found in the host. Using complementary in vivo zebrafish and in vitro macrophage cell culture models of Cryptococcus infection, we found that these eicosanoids manipulate host innate immune cells by activating the host receptor PPAR-gamma which is an important regulator of macrophage inflammatory phenotypes. We initially identified PGE2 as the eicosanoid species responsible for this effect; however, we later found that a derivative of PGE2-15-keto-PGE2-was ultimately responsible and that this eicosanoid acted as a partial agonist to PPAR-gamma. In this commentary, we will discuss some of the concepts and conclusions in our original publication and expand on their implications and future directions.
Insights
The fungus Cryptococcus neoformans mimics host eicosanoids to manipulate immune cells. It activates the PPAR-gamma receptor, impacting macrophage inflammation.
Area of Science:
- Immunology
- Mycology
- Molecular Biology
Background:
- * Cryptococcus neoformans is a fungal pathogen that causes cryptococcosis.
- * Host immune responses are crucial for controlling fungal infections.
- * Eicosanoids are signaling molecules involved in inflammation and immune regulation.
Purpose of the Study:
- * To investigate the mechanism by which Cryptococcus neoformans manipulates host cells.
- * To identify the specific molecules produced by the fungus that mediate this manipulation.
- * To understand how these fungal molecules affect host innate immune cells.
Main Methods:
- * In vivo infection model using zebrafish.
- * In vitro macrophage cell culture model.
- * Analysis of eicosanoid production and host receptor activation.
Main Results:
- * Cryptococcus neoformans produces eicosanoids that mimic host molecules.
- * These fungal eicosanoids activate the host receptor PPAR-gamma.
- * 15-keto-PGE2 was identified as the key eicosanoid, acting as a partial agonist to PPAR-gamma.
Conclusions:
- * Fungal eicosanoids are a novel mechanism for immune evasion by Cryptococcus neoformans.
- * Activation of PPAR-gamma by fungal eicosanoids modulates macrophage inflammatory responses.
- * This study opens new avenues for therapeutic strategies targeting fungal manipulation of host immunity.
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