Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

Abstract Cryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where i...

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Autores principales:	Benjamin N. Nelson, Savannah G. Beakley, Sierra Posey, Brittney Conn, Emma Maritz, Janakiram Seshu, Karen L. Wozniak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2941d43f4945448b9b9cafcb8662529f
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spelling	oai:doaj.org-article:2941d43f4945448b9b9cafcb8662529f2021-12-02T14:33:51ZAntifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans10.1038/s41598-021-92991-62045-2322https://doaj.org/article/2941d43f4945448b9b9cafcb8662529f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92991-6https://doaj.org/toc/2045-2322Abstract Cryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.Benjamin N. NelsonSavannah G. BeakleySierra PoseyBrittney ConnEmma MaritzJanakiram SeshuKaren L. WozniakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin N. Nelson Savannah G. Beakley Sierra Posey Brittney Conn Emma Maritz Janakiram Seshu Karen L. Wozniak Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
description	Abstract Cryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.
format	article
author	Benjamin N. Nelson Savannah G. Beakley Sierra Posey Brittney Conn Emma Maritz Janakiram Seshu Karen L. Wozniak
author_facet	Benjamin N. Nelson Savannah G. Beakley Sierra Posey Brittney Conn Emma Maritz Janakiram Seshu Karen L. Wozniak
author_sort	Benjamin N. Nelson
title	Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_short	Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_full	Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_fullStr	Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_full_unstemmed	Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_sort	antifungal activity of dendritic cell lysosomal proteins against cryptococcus neoformans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2941d43f4945448b9b9cafcb8662529f
work_keys_str_mv	AT benjaminnnelson antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT savannahgbeakley antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT sierraposey antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT brittneyconn antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT emmamaritz antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT janakiramseshu antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans AT karenlwozniak antifungalactivityofdendriticcelllysosomalproteinsagainstcryptococcusneoformans
_version_	1718391118475821056

Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

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