Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils

Serial passaging of the human fungal pathogen Candida albicans in the gastrointestinal tract of antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect the host from infection by a wide range of pathogens via trained immunity. Here, we further investigate...

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Autores principales:	Jose Antonio Reales-Calderon, Gloria H. W. Tso, Alrina S. M. Tan, Pei Xiang Hor, Julia Böhme, Karen W. W. Teng, Evan W. Newell, Amit Singhal, Norman Pavelka
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Candida albicans neutrophils trained immunity infectious diseases live attenuated vaccines immunometabolism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b78244ca41df4506bafd59ca00f923e2
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spelling	oai:doaj.org-article:b78244ca41df4506bafd59ca00f923e22021-11-22T06:31:11ZGut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils2235-298810.3389/fcimb.2021.743735https://doaj.org/article/b78244ca41df4506bafd59ca00f923e22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.743735/fullhttps://doaj.org/toc/2235-2988Serial passaging of the human fungal pathogen Candida albicans in the gastrointestinal tract of antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect the host from infection by a wide range of pathogens via trained immunity. Here, we further investigated the molecular and cellular mechanisms underlying this innate immune memory. Both Dectin-1 (the main receptor for β-glucan; a well-described immune training molecule in the fungal cell wall) and Nod2 (a receptor described to mediate BCG-induced trained immunity), were redundant for the protection induced by gut-evolved C. albicans against a virulent C. albicans strain, suggesting that gut-evolved C. albicans strains induce trained immunity via other pathways. Cytometry by time of flight (CyTOF) analysis of mouse splenocytes revealed that immunization with gut-evolved C. albicans resulted in an expansion of neutrophils and a reduction in natural killer (NK) cells, but no significant numeric changes in monocytes, macrophages or dendritic cell populations. Systemic depletion of phagocytes or neutrophils, but not of macrophages or NK cells, reduced protection mediated by gut-evolved C. albicans. Splenocytes and bone marrow cells of mice immunized with gut-evolved C. albicans demonstrated metabolic changes. In particular, splenic neutrophils displayed significantly elevated glycolytic and respiratory activity in comparison to those from mock-immunized mice. Although further investigation is required for fully deciphering the trained immunity mechanism induced by gut-evolved C. albicans strains, this data is consistent with the existence of several mechanisms of trained immunity, triggered by different training stimuli and involving different immune molecules and cell types.Jose Antonio Reales-CalderonGloria H. W. TsoAlrina S. M. TanPei Xiang HorJulia BöhmeKaren W. W. TengEvan W. NewellAmit SinghalAmit SinghalNorman PavelkaFrontiers Media S.A.articleCandida albicansneutrophilstrained immunityinfectious diseaseslive attenuated vaccinesimmunometabolismMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans neutrophils trained immunity infectious diseases live attenuated vaccines immunometabolism Microbiology QR1-502
spellingShingle	Candida albicans neutrophils trained immunity infectious diseases live attenuated vaccines immunometabolism Microbiology QR1-502 Jose Antonio Reales-Calderon Gloria H. W. Tso Alrina S. M. Tan Pei Xiang Hor Julia Böhme Karen W. W. Teng Evan W. Newell Amit Singhal Amit Singhal Norman Pavelka Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
description	Serial passaging of the human fungal pathogen Candida albicans in the gastrointestinal tract of antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect the host from infection by a wide range of pathogens via trained immunity. Here, we further investigated the molecular and cellular mechanisms underlying this innate immune memory. Both Dectin-1 (the main receptor for β-glucan; a well-described immune training molecule in the fungal cell wall) and Nod2 (a receptor described to mediate BCG-induced trained immunity), were redundant for the protection induced by gut-evolved C. albicans against a virulent C. albicans strain, suggesting that gut-evolved C. albicans strains induce trained immunity via other pathways. Cytometry by time of flight (CyTOF) analysis of mouse splenocytes revealed that immunization with gut-evolved C. albicans resulted in an expansion of neutrophils and a reduction in natural killer (NK) cells, but no significant numeric changes in monocytes, macrophages or dendritic cell populations. Systemic depletion of phagocytes or neutrophils, but not of macrophages or NK cells, reduced protection mediated by gut-evolved C. albicans. Splenocytes and bone marrow cells of mice immunized with gut-evolved C. albicans demonstrated metabolic changes. In particular, splenic neutrophils displayed significantly elevated glycolytic and respiratory activity in comparison to those from mock-immunized mice. Although further investigation is required for fully deciphering the trained immunity mechanism induced by gut-evolved C. albicans strains, this data is consistent with the existence of several mechanisms of trained immunity, triggered by different training stimuli and involving different immune molecules and cell types.
format	article
author	Jose Antonio Reales-Calderon Gloria H. W. Tso Alrina S. M. Tan Pei Xiang Hor Julia Böhme Karen W. W. Teng Evan W. Newell Amit Singhal Amit Singhal Norman Pavelka
author_facet	Jose Antonio Reales-Calderon Gloria H. W. Tso Alrina S. M. Tan Pei Xiang Hor Julia Böhme Karen W. W. Teng Evan W. Newell Amit Singhal Amit Singhal Norman Pavelka
author_sort	Jose Antonio Reales-Calderon
title	Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
title_short	Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
title_full	Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
title_fullStr	Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
title_full_unstemmed	Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils
title_sort	gut-evolved candida albicans induces metabolic changes in neutrophils
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b78244ca41df4506bafd59ca00f923e2
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Gut-Evolved Candida albicans Induces Metabolic Changes in Neutrophils

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