title: Candida albicans escapes from mouse neutrophils.
abstract: Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On the contrary, growth and subsequent escape of C. albicans are blocked inside human neutrophils. According to our findings, this blockage in human neutrophils might be a result of higher levels of MPO activity and the presence of α-defensins. We therefore outline differences in antifungal immune defense between humans and mouse strains, which facilitates a more accurate interpretation of in vivo results.
authors: Laboratory for Molecular Infection Medicine Sweden, Umeå Centre for Microbial Research, Umeå University, Sjukhusområdet 6C, 90185 Umeå, Sweden.
authors: David
authors: D
authors: Ermert
authors: Maria J
authors: MJ
authors: Niemiec
authors: Marc
authors: M
authors: Röhm
authors: Andreas
authors: A
authors: Glenthøj
authors: Niels
authors: N
authors: Borregaard
authors: Constantin F
authors: CF
authors: Urban
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology*; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D057131:Immune Evasion; D007113:Immunity, Innate; D008297:Male; D051379:Mice / Q000276:immunology*; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D009195:Peroxidase / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D016897:Respiratory Burst; D013045:Species Specificity; D023084:alpha-Defensins / Q000235:genetics / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; D009195:Peroxidase
keywords: defensins; immune evasion; killing; myeloperoxidase