The fungal pathogen Cryptococcus neoformans manipulates macrophage phagosome maturation.
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.
Institute of Microbiology and Infection and School of Biosciences, University of Birmingham, Birmingham, UK.
Leanne M
LM
Smith
Emily F
EF
Dixon
Robin C
RC
May
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006863:Hydrogen-Ion Concentration; D057131:Immune Evasion; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D010588:Phagosomes / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*; D020691:rab GTP-Binding Proteins / Q000032:analysis; D020696:rab5 GTP-Binding Proteins / Q000032:analysis; D000099193:rab11 GTP-Binding Proteins
D002118:Calcium; D010447:Peptide Hydrolases; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins