Imaging invasive fungal growth and inflammation in NADPH oxidase-deficient zebrafish

Abstract

28Neutrophils are primary cells of the innate immune system that generate reactive oxygen species 29 (ROS) and mediate host defense. Deficient phagocyte NADPH oxidase (PHOX) function leads to 30 chronic granulomatous disease (CGD) that is characterized by invasive infections including those 31 by the generally non-pathogenic fungus Aspergillus nidulans. The role of neutrophil ROS in this 32 specific host-pathogen interaction remains unclear. Here, we exploit the optical transparency of 33 zebrafish to image the effects of neutrophil ROS on invasive fungal growth and neutrophil 34 behavior in response to Aspergillus nidulans. In a wild-type host, A. nidulans germinates rapidly 35 and elicits a robust inflammatory response with efficient fungal clearance. PHOX-deficient larvae 36 have increased susceptibility to invasive A. nidulans infection despite robust neutrophil infiltration. 37