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Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease

Coccidioides is a soil-borne fungal pathogen and causative agent of a human respiratory disease (coccidioidomycosis) endemic to semi-desert regions of southwestern United States, Mexico, Central and South America. Aerosolized arthroconidia inhaled by the mammalian host first undergo conversion to la...

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Autores principales: Peláez-Jaramillo, Carlos Alberto, Jiménez-Alzate, Maria Del Pilar, Araque-Marin, Pedronel, Hung, Chiung-Yu, Castro-Lopez, Natalia, Cole, Garry T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155295/
https://www.ncbi.nlm.nih.gov/pubmed/34055661
http://dx.doi.org/10.3389/fcimb.2021.592826
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author Peláez-Jaramillo, Carlos Alberto
Jiménez-Alzate, Maria Del Pilar
Araque-Marin, Pedronel
Hung, Chiung-Yu
Castro-Lopez, Natalia
Cole, Garry T.
author_facet Peláez-Jaramillo, Carlos Alberto
Jiménez-Alzate, Maria Del Pilar
Araque-Marin, Pedronel
Hung, Chiung-Yu
Castro-Lopez, Natalia
Cole, Garry T.
author_sort Peláez-Jaramillo, Carlos Alberto
collection PubMed
description Coccidioides is a soil-borne fungal pathogen and causative agent of a human respiratory disease (coccidioidomycosis) endemic to semi-desert regions of southwestern United States, Mexico, Central and South America. Aerosolized arthroconidia inhaled by the mammalian host first undergo conversion to large parasitic cells (spherules, 80–100 μm diameter) followed by endosporulation, a process by which the contents of spherules give rise to multiple endospores. The latter are released upon rupture of the maternal spherules and establish new foci of lung infection. A novel feature of spherule maturation prior to endosporulation is the secretion of a lipid-rich, membranous cell surface layer shed in vivo during growth of the parasitic cells and secretion into liquid culture medium during in vitro growth. Chemical analysis of the culture derived spherule outer wall (SOW) fraction showed that it is composed largely of phospholipids and is enriched with saturated fatty acids, including myristic, palmitic, elaidic, oleic, and stearic acid. NMR revealed the presence of monosaccharide- and disaccharide-linked acylglycerols and sphingolipids. The major sphingolipid components are sphingosine and ceramide. Primary neutrophils derived from healthy C57BL/6 and DBA/2 mice incubated with SOW lipids revealed a significant reduction in fungicidal activity against viable Coccidioides arthroconidia compared to incubation of neutrophils with arthroconidia alone. Host cell exposure to SOW lipids had no effect on neutrophil viability. Furthermore, C57BL/6 mice that were challenged subcutaneously with Coccidioides arthroconidia in the presence of the isolated SOW fraction developed disseminated disease, while control mice challenged with arthroconidia alone by the same route showed no dissemination of infection. We hypothesize that SOW lipids contribute to suppression of inflammatory response to Coccidioides infection. Studies are underway to characterize the immunosuppressive mechanism(s) of SOW lipids.
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spelling pubmed-81552952021-05-28 Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease Peláez-Jaramillo, Carlos Alberto Jiménez-Alzate, Maria Del Pilar Araque-Marin, Pedronel Hung, Chiung-Yu Castro-Lopez, Natalia Cole, Garry T. Front Cell Infect Microbiol Cellular and Infection Microbiology Coccidioides is a soil-borne fungal pathogen and causative agent of a human respiratory disease (coccidioidomycosis) endemic to semi-desert regions of southwestern United States, Mexico, Central and South America. Aerosolized arthroconidia inhaled by the mammalian host first undergo conversion to large parasitic cells (spherules, 80–100 μm diameter) followed by endosporulation, a process by which the contents of spherules give rise to multiple endospores. The latter are released upon rupture of the maternal spherules and establish new foci of lung infection. A novel feature of spherule maturation prior to endosporulation is the secretion of a lipid-rich, membranous cell surface layer shed in vivo during growth of the parasitic cells and secretion into liquid culture medium during in vitro growth. Chemical analysis of the culture derived spherule outer wall (SOW) fraction showed that it is composed largely of phospholipids and is enriched with saturated fatty acids, including myristic, palmitic, elaidic, oleic, and stearic acid. NMR revealed the presence of monosaccharide- and disaccharide-linked acylglycerols and sphingolipids. The major sphingolipid components are sphingosine and ceramide. Primary neutrophils derived from healthy C57BL/6 and DBA/2 mice incubated with SOW lipids revealed a significant reduction in fungicidal activity against viable Coccidioides arthroconidia compared to incubation of neutrophils with arthroconidia alone. Host cell exposure to SOW lipids had no effect on neutrophil viability. Furthermore, C57BL/6 mice that were challenged subcutaneously with Coccidioides arthroconidia in the presence of the isolated SOW fraction developed disseminated disease, while control mice challenged with arthroconidia alone by the same route showed no dissemination of infection. We hypothesize that SOW lipids contribute to suppression of inflammatory response to Coccidioides infection. Studies are underway to characterize the immunosuppressive mechanism(s) of SOW lipids. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8155295/ /pubmed/34055661 http://dx.doi.org/10.3389/fcimb.2021.592826 Text en Copyright © 2021 Peláez-Jaramillo, Jiménez-Alzate, Araque-Marin, Hung, Castro-Lopez and Cole https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Peláez-Jaramillo, Carlos Alberto
Jiménez-Alzate, Maria Del Pilar
Araque-Marin, Pedronel
Hung, Chiung-Yu
Castro-Lopez, Natalia
Cole, Garry T.
Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title_full Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title_fullStr Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title_full_unstemmed Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title_short Lipid Secretion by Parasitic Cells of Coccidioides Contributes to Disseminated Disease
title_sort lipid secretion by parasitic cells of coccidioides contributes to disseminated disease
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155295/
https://www.ncbi.nlm.nih.gov/pubmed/34055661
http://dx.doi.org/10.3389/fcimb.2021.592826
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