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PLoS Biol. 2019 Sep 4;17(9):e3000113. doi: 10.1371/journal.pbio.3000113. eCollection 2019 Sep.

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

Author information

1
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
2
Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
3
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
4
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
5
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
6
Monash Micro Imaging, Monash University, Clayton, Victoria, Australia.
7
Genetics, Genomics and Systems Biology, School of BioSciences, University of Melbourne, Parkville, Victoria, Australia.
8
School of Mathematics, Computer Science and Engineering, City University of London, London, United Kingdom.

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, and involves alterations of phagocyte mobility, intercellular tethering, and phagosome transfer. Shuttling kinetics were fungal-species-specific, implicating a fungal determinant. β-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 favorable macrophage intracellular niche. Shuttling is a frequent host-pathogen interaction contributing to fungal infection establishment patterns.

Conflict of interest statement

The authors have declared that no competing interests exist.

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