Histoplasma capsulatum‐induced extracellular DNA trap release in human neutrophils
Neutrophils are leukocytes that are capable of eliminating both intra‐ and extracellular pathogens by mechanisms such as phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). Histoplasma capsulatum var. capsulatum (H. capsulatum) is a dimorphic fungus with a global distr...
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Published in | Cellular microbiology Vol. 22; no. 7; pp. e13195 - n/a |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Inc
01.07.2020
Hindawi Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Neutrophils are leukocytes that are capable of eliminating both intra‐ and extracellular pathogens by mechanisms such as phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). Histoplasma capsulatum var. capsulatum (H. capsulatum) is a dimorphic fungus with a global distribution that causes histoplasmosis, a disease that is endemic in different geographic areas and is spreading worldwide. The release of NETs has been described as an important host defense mechanism against different fungi; however, there are no reports demonstrating that this process is implicated in neutrophil response to H. capsulatum infection. Therefore, the aim of this work is to investigate whether isolated human neutrophils release NETs in response to H. capsulatum and the potential mechanisms involved, as well as delineate the NETs antifungal activity. Using both confocal fluorescence and scanning electron microscopy techniques, we determined that NETs are released in vitro in response to H. capsulatum via an oxidative mechanism that is downstream of activation of the Syk and Src kinase pathways and is also dependent on CD18. NETs released in response to H. capsulatum yeasts involve the loss of neutrophil viability and are associated with elastase and citrullinated histones, however also can occur in a PAD4 histone citrullination independent pathway. This NETs also presented fungicidal activity against H. capsulatum yeasts. Our findings may contribute to the understanding of how neutrophils recognize and respond as immune effector cells to H. capsulatum, which may lead to better knowledge of histoplasmosis pathophysiology and treatment. |
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Bibliography: | Funding information Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 309734/2018‐5, 434914/2018‐5, 409057/2018‐5, 309216/2017‐6; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Grant/Award Number: E‐26/203.312/2017; Fundação de Amparo à Pesquisa do Estado de Minas Gerais ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1462-5814 1462-5822 |
DOI: | 10.1111/cmi.13195 |