Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus

PLoS Pathogens

Julianne Jorgensen¹  Felix Ellett¹  Galit H. Frydman¹  Daniel Irimia¹  Caroline N. Jones² 

[1] BioMEMS Resource Center, Division of Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Massachusetts, United States of America;Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

关键词: Neutrophils;    Microfluidics;    Aspergillus fumigatus;    Platelets;    Chelation;    Fungal diseases;    Immune cells;    Fungi;   

DOI  :  10.1371/journal.ppat.1006154

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. Investigations of neutrophil-hypha interaction in vitro and in animal models of IA are limited by lack of temporal and spatial control over interactions. This study presents a new approach for studying neutrophil-hypha interaction at single cell resolution over time, which revealed an evasive fungal behavior triggered by interaction with neutrophils: Interacting hyphae performed de novo tip formation to generate new hyphal branches, allowing the fungi to avoid the interaction point and continue invasive growth. Induction of this mechanism was independent of neutrophil NADPH oxidase activity and neutrophil extracellular trap (NET) formation, but could be phenocopied by iron chelation and mechanical or physiological stalling of hyphal tip extension. The consequence of branch induction upon interaction outcome depends on the number and activity of neutrophils available: In the presence of sufficient neutrophils branching makes hyphae more vulnerable to destruction, while in the presence of limited neutrophils the interaction increases the number of hyphal tips, potentially making the infection more aggressive. This has direct implications for infections in neutrophil-deficient patients and opens new avenues for treatments targeting fungal branching.

【 授权许可】

CC BY