The fungal pathogen Cryptococcus neoformans manipulates macrophage phagosome maturation

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.

Abstract

Phagocytosis by cells of the innate immune system, such as macrophages, and the subsequent successful maturation of the phagosome, is key for the clearance of pathogens. The fungal pathogen Cryptococcus neoformans is known to overcome killing by host phagocytes and both replicate within these cells and also escape via a non-lytic process termed vomocytosis. Here we demonstrate that, during intracellular growth, cryptococci modify phagolysosome maturation. Live cryptococci, but not heat-killed pathogens or inert targets, induce the premature removal of the early phagosome markers Rab5 and Rab11. In addition, significant acidification of the phagosome, calcium flux and protease activity is hindered, thus rendering the phagosome permissive for cryptococcal proliferation. Interestingly, several attenuated cryptococcal mutants retain this ability to subvert phagosomal maturation, suggesting that hitherto unidentified pathogen mechanisms regulate this process.

Details

Original languageEnglish
Pages (from-to)702–713
JournalCellular Microbiology
Volume17
Issue number5
Early online date19 Dec 2014
Publication statusPublished - 17 Apr 2015