Open AccessHistoplasma capsulatum ‐induced extracellular DNA trap release in human neutrophils
Author(s) -
ThompsonSouza Glaucia A.,
Santos Giulia M. P.,
Silva Juliana C.,
Muniz Valdirene S.,
Braga Yasmim A. V.,
Figueiredo Rodrigo T.,
Melo Rossana C. N.,
Santos André L. S.,
Pinto Marcia R.,
Neves Josiane S.
Publication year - 2020
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13195
Subject(s) - neutrophil extracellular traps , biology , histoplasma , microbiology and biotechnology , degranulation , dimorphic fungus , extracellular , candida albicans , innate immune system , effector , immune system , immunology , histoplasmosis , inflammation , histoplasma capsulatum , biochemistry , receptor , yeast
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.