English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Cryptococcus neoformans  is one of the leading causes of invasive fungal infection in humans worldwide.  C .  neoformans  uses macrophages as a proliferative niche to increase infective burden and avoid immune surveillance. However, the specific mechanisms by which  C .  neoformans  manipulates host immunity to promote its growth during infection remain ill-defined. Here we demonstrate that eicosanoid lipid mediators manipulated and/or produced by  C .  neoformans  play a key role in regulating pathogenesis.  C .  neoformans  is known to secrete several eicosanoids that are highly similar to those found in vertebrate hosts. Using eicosanoid deficient cryptococcal mutants  Δplb1  and  Δlac1 , we demonstrate that prostaglandin E 2  is required by  C .  neoformans  for proliferation within macrophages and  in vivo  during infection. Genetic and pharmacological disruption of host PGE 2  synthesis is not required for promotion of cryptococcal growth by eicosanoid production. We find that PGE 2  must be dehydrogenated into 15-keto-PGE 2  to promote fungal growth, a finding that implicated the host nuclear receptor PPAR-γ.  C .  neoformans  infection of macrophages activates host PPAR-γ and its inhibition is sufficient to abrogate the effect of 15-keto-PGE 2  in promoting fungal growth during infection. Thus, we describe the first mechanism of reliance on pathogen-derived eicosanoids in fungal pathogenesis and the specific role of 15-keto-PGE 2  and host PPAR-γ in cryptococcosis.

plos pathogens

15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection