Macrophage mitochondrial and stress response to ingestion of Cryptococcus neoformans

Carolina Coelho, Ana Camila Oliveira Souza, Lorena Da Silveira Derengowski, Carlos De Leon-Rodriguez, Bo Wang, Rosiris Leon-Rivera, Anamelia Lorenzetti Bocca, Teresa Gonçalves, Arturo Casadevall

Research output: Contribution to journalArticlepeer-review

Abstract

Human infection with Cryptococcus neoformans, a common fungal pathogen, follows deposition of yeast spores in the lung alveoli. The subsequent host-pathogen interaction can result in eradication, latency, or extrapulmonary dissemination. Successful control of C. neoformans infection is dependent on host macrophages, but macrophages display little ability to kill C. neoformans in vitro. Recently, we reported that ingestion of C. neoformans by mouse macrophages induces early cell cycle progression followed by mitotic arrest, an event that almost certainly reflects host cell damage. The goal of the present work was to understand macrophage pathways affected by C. neoformans toxicity. Infection of macrophages by C. neoformans was associated with alterations in protein translation rate and activation of several stress pathways, such as hypoxia-inducing factor-1-α, receptor-interacting protein 1, and apoptosis-inducing factor. Concomitantly we observed mitochondrial depolarization in infected macrophages, an observation that was replicated in vivo. We also observed differences in the stress pathways activated, depending on macrophage cell type, consistent with the nonspecific nature of C. neoformans virulence known to infect phylogenetically distant hosts. Our results indicate that C. neoformans infection impairs multiple host cellular functions and undermines the health of these critical phagocytic cells, which can potentially interfere with their ability to clear this fungal pathogen.

Original languageEnglish (US)
Pages (from-to)2345-2357
Number of pages13
JournalJournal of Immunology
Volume194
Issue number5
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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