β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

Pazhakh, V.; Ellett, F.; O'Donnell, J.; Pase, L.; Schulze, K. E.; Greulich, R. S.; Reyes-Aldasoro, C. C.; Croker, B. A.; Andrianopoulos, A.; Lieschke, G. J.

doi:10.1101/512228

bioRxiv · 10.1101/512228

β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

Pazhakh, V.·Ellett, F.·O'Donnell, J.·Pase, L.·Schulze, K. E.·Greulich, R. S.·Reyes-Aldasoro, C. C.·Croker, B. A.·Andrianopoulos, A.·Lieschke, G. J.

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Abstract

The initial host response to fungal pathogen invasion is critical to infection establishment and outcome. However, the diversity of leukocyte-pathogen interactions is only recently being appreciated. We describe a new form of interleukocyte conidial exchange called \"shuttling\". In Talaromyces marneffei and Aspergillus fumigatus zebrafish in vivo infections, live imaging demonstrated conidia initially phagocytosed by neutrophils were transferred to macrophages. Shuttling is unidirectional, not a chance event, involves alterations of phagocyte mobility, inter-cellular tethering, and phagosome transfer. Shuttling kinetics were fungal species-specific, implicating a fungal determinant. {beta}-glucan serves as a fungal-derived signal sufficient for shuttling. Murine phagocytes also shuttled in vitro. The impact of shuttling for microbiological outcomes of in vivo infections is difficult to specifically assess experimentally, but for these two pathogens, shuttling augments initial conidial redistribution away from fungicidal neutrophils into the favourable macrophage intracellular niche. Shuttling is a frequent host/pathogen interaction contributing to fungal infection establishment patterns.

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Pazhakh, V., Ellett, F., O'Donnell, J., Pase, L., Schulze, K. E., Greulich, R. S., Reyes-Aldasoro, C. C., Croker, B. A., Andrianopoulos, A., Lieschke, G. J.. 2019-01-04. β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment. https://doi.org/10.1101/512228

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