PPAR-gamma Fun(gi) With Prostaglandin.

Robert J Evans,Simon A Johnston

doi:10.1177/1550762919899641

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.

Highlights

Cryptococcus neoformans is a pathogenic fungus that is ubiquitous in our everyday environment, but only those with severe or unusual immune deficiencies, such as HIV AIDS, develop serious disease.[1]
To kill Cryptococcus, macrophages must be activated by a Th1 CD4+ T-cell-mediated adaptive immune response[3]; failure to control intracellular infection can lead to dissemination from the lungs into the central nervous system and the development of fatal fungal meningitis
Cryptococcus can produce a number of eicosanoid species which closely resemble those found in the host but natural purpose of these lipids normally associated with cell to cell signaling in multicellular organisms is unknown.[6]

Summary

Introduction

Cryptococcus neoformans is a pathogenic fungus that is ubiquitous in our everyday environment, but only those with severe or unusual immune deficiencies, such as HIV AIDS, develop serious disease.[1]. Keywords Cryptococcus neoformans, fungal infection, host pathogen interactions, macrophages, zebrafish, eicosanoids, 15-keto-PGE , PPAR-gamma 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection.

Results

Conclusion