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Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

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 kill...

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Autores principales: Nelson, Benjamin N., Beakley, Savannah G., Posey, Sierra, Conn, Brittney, Maritz, Emma, Seshu, Janakiram, Wozniak, Karen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245489/
https://www.ncbi.nlm.nih.gov/pubmed/34193926
http://dx.doi.org/10.1038/s41598-021-92991-6
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author Nelson, Benjamin N.
Beakley, Savannah G.
Posey, Sierra
Conn, Brittney
Maritz, Emma
Seshu, Janakiram
Wozniak, Karen L.
author_facet Nelson, Benjamin N.
Beakley, Savannah G.
Posey, Sierra
Conn, Brittney
Maritz, Emma
Seshu, Janakiram
Wozniak, Karen L.
author_sort Nelson, Benjamin N.
collection PubMed
description 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.
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spelling pubmed-82454892021-07-06 Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans Nelson, Benjamin N. Beakley, Savannah G. Posey, Sierra Conn, Brittney Maritz, Emma Seshu, Janakiram Wozniak, Karen L. Sci Rep Article 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. Nature Publishing Group UK 2021-06-30 /pmc/articles/PMC8245489/ /pubmed/34193926 http://dx.doi.org/10.1038/s41598-021-92991-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nelson, Benjamin N.
Beakley, Savannah G.
Posey, Sierra
Conn, Brittney
Maritz, Emma
Seshu, Janakiram
Wozniak, Karen L.
Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title 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_short Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans
title_sort antifungal activity of dendritic cell lysosomal proteins against cryptococcus neoformans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245489/
https://www.ncbi.nlm.nih.gov/pubmed/34193926
http://dx.doi.org/10.1038/s41598-021-92991-6
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