Abstract
Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.
Highlights
Dissemination of pathogens from a primary site of colonization or infection can occur via different routes, including lymphatic vessels and the blood stream [1]
The fate of C. albicans upon exposure to murine blood was analyzed in whole blood collected from two of the most commonly used mouse strains for infection experiments, BALB/c and C57BL/6J
As described by Hünniger et al for the human whole-blood model [4], whole blood was inoculated with 1 × 106/ml of yeast-grown C. albicans and fungal survival was determined by counting colony forming units (CFU) at various time points over a time course of 3 h
Summary
Dissemination of pathogens from a primary site of colonization or infection can occur via different routes, including lymphatic vessels and the blood stream [1]. If bacteremia or fungemia occurs transiently or intermittingly, pathogens might not be detectable in every blood sample during hematogenous dissemination [3]. We previously established an ex vivo human whole-blood infection model that allowed us to define which immune cells interact with the human fungal pathogen Candida albicans [4], to identify cross-talk between different components of the host response [5], and to detect substantial differences between related fungal pathogens [6]
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