Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus
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 ani...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2017
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| Online Access: | http://hdl.handle.net/1721.1/110043 https://orcid.org/0000-0002-8126-8580 |
| _version_ | 1826204134699696128 |
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| author | Ellett, Felix Jorgensen, Julianne Jones, Caroline N. Irimia, Daniel Frydman, Galit |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Ellett, Felix Jorgensen, Julianne Jones, Caroline N. Irimia, Daniel Frydman, Galit |
| author_sort | Ellett, Felix |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:49:27Z |
| format | Article |
| id | mit-1721.1/110043 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:49:27Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1100432022-09-28T10:17:32Z Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus Ellett, Felix Jorgensen, Julianne Jones, Caroline N. Irimia, Daniel Frydman, Galit Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Frydman, Galit 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. United States. National Institutes of Health (EB002503) United States. National Institutes of Health (GM092804) 2017-06-20T14:00:36Z 2017-06-20T14:00:36Z 2017-01 2016-11 Article http://purl.org/eprint/type/JournalArticle 1553-7374 http://hdl.handle.net/1721.1/110043 Ellett, Felix; Jorgensen, Julianne; Frydman, Galit H.; Jones, Caroline N. and Irimia, Daniel. “Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus Fumigatus.” Edited by Xiaorong Lin. PLOS Pathogens 13, no. 1 (January 2017): e1006154 © 2017 Ellett et al https://orcid.org/0000-0002-8126-8580 en_US http://dx.doi.org/10.1371/journal.ppat.1006154 PLoS Pathogens Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | Ellett, Felix Jorgensen, Julianne Jones, Caroline N. Irimia, Daniel Frydman, Galit Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title | Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title_full | Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title_fullStr | Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title_full_unstemmed | Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title_short | Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus |
| title_sort | neutrophil interactions stimulate evasive hyphal branching by aspergillus fumigatus |
| url | http://hdl.handle.net/1721.1/110043 https://orcid.org/0000-0002-8126-8580 |
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