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

Vahid Pazhakh,Keith E Schulze,Alex Andrianopoulos,Luke Pase,Joanne A O’Donnell,Felix Ellett,Constantino Carlos Reyes-Aldasoro,Graham J Lieschke,Ben A Croker,Aakash Gupta,R Stefan Greulich,Aaron P Mitchell

doi:10.1371/journal.pbio.3000113

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.

Highlights

In vertebrates, two phagocytic cell types have long been recognized as key players in the initial host defense response to infection: neutrophil granulocytes and macrophages [1]
Some T. marneffei conidia phagocytosed by neutrophils are “shuttled” to macrophages
We have previously examined phagocytosis during infection establishment and previously reported that macrophage phagocytosis predominates over neutrophil phagocytosis in the first 3 h following inoculation [20]

Summary

Introduction

Two phagocytic cell types have long been recognized as key players in the initial host defense response to infection: neutrophil granulocytes and macrophages [1]. Irimia, he was supported by the Massachusetts General Hospital BioMEMS Center (National Institutes of Health Grant EB002503). A Dora Lush Scholarship (National Health and Medical Research Council) supported JO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion