Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus. 2017

Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
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.

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.

UI MeSH Term Description Entries
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001228 Aspergillosis Infections with fungi of the genus ASPERGILLUS. Aspergillus Infection,Aspergilloses,Aspergillus Infections,Infection, Aspergillus,Infections, Aspergillus
D001232 Aspergillus fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus fumigates,Neosartorya fumigata,Sartorya fumigata
D016867 Immunocompromised Host A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Immunosuppressed Host,Immunocompromised Patient,Host, Immunocompromised,Host, Immunosuppressed,Hosts, Immunocompromised,Hosts, Immunosuppressed,Immunocompromised Hosts,Immunocompromised Patients,Immunosuppressed Hosts,Patient, Immunocompromised,Patients, Immunocompromised
D019255 NADPH Oxidases A family of membrane-associated flavoprotein NADPH-dependent oxidoreductases that catalyze the univalent reduction of OXYGEN to create SUPEROXIDES. Structurally, they are characterized by six N-terminal transmembrane ALPHA-HELICES, a FLAVIN-ADENINE DINUCLEOTIDE (FAD)-binding region, and a C-terminal NADPH-binding region. They are expressed primarily by EPITHELIAL CELLS in gut, kidney, colon, and smooth muscle tissues, as well as GRANULOCYTES and function to transfer electrons across membranes to molecular oxygen. Defects in the production of superoxide ions by some NADPH oxidases result in GRANULOMATOUS DISEASE, CHRONIC. NADPH Oxidase,NAD(P)H Oxidases,NAD(P)H oxidase,Nox Proteins,Oxidase, NADPH,Oxidases, NADPH
D025301 Hyphae Microscopic threadlike filaments in FUNGI that are filled with a layer of protoplasm. Collectively, the hyphae make up the MYCELIUM. Hypha,Hyphas
D065206 Extracellular Traps Extracellular structure primarily composed of CHROMATIN and associated PROTEASES. Neutrophil Extracellular Traps,EEDTs (Eosinophil Extracellular DNA Traps),Eosinophil Extracellular DNA Traps,Eosinophil Extracellular Traps,Extracellular DNA Traps,NETs (Neutrophil Extracellular Traps),DNA Trap, Extracellular,DNA Traps, Extracellular,EEDT (Eosinophil Extracellular DNA Traps),Eosinophil Extracellular Trap,Extracellular DNA Trap,Extracellular Trap,Extracellular Trap, Eosinophil,Extracellular Trap, Neutrophil,Extracellular Traps, Eosinophil,Extracellular Traps, Neutrophil,NET (Neutrophil Extracellular Traps),Neutrophil Extracellular Trap,Trap, Eosinophil Extracellular,Trap, Extracellular,Trap, Extracellular DNA,Trap, Neutrophil Extracellular,Traps, Eosinophil Extracellular,Traps, Extracellular,Traps, Extracellular DNA,Traps, Neutrophil Extracellular

Related Publications

Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
February 1990, Journal of leukocyte biology,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
January 2016, Journal of immunology (Baltimore, Md. : 1950),
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
September 2013, Antimicrobial agents and chemotherapy,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
December 2005, Medical mycology,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
December 2012, Annals of the New York Academy of Sciences,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
January 2023, bioRxiv : the preprint server for biology,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
May 2023, PLoS pathogens,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
May 2016, Infection and immunity,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
December 2014, Mycopathologia,
Felix Ellett, and Julianne Jorgensen, and Galit H Frydman, and Caroline N Jones, and Daniel Irimia
April 2009, Eukaryotic cell,
Copied contents to your clipboard!