Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.

It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known abou...

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Autores principales:	Katherine M Still, Samantha J Batista, Carleigh A O'Brien, Oyebola O Oyesola, Simon P Früh, Lauren M Webb, Igor Smirnov, Michael A Kovacs, Maureen N Cowan, Nikolas W Hayes, Jeremy A Thompson, Elia D Tait Wojno, Tajie H Harris
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/15e74006523b4a4c8331d34646726ea9
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spelling	oai:doaj.org-article:15e74006523b4a4c8331d34646726ea92021-12-02T19:59:54ZAstrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.1553-73661553-737410.1371/journal.ppat.1009027https://doaj.org/article/15e74006523b4a4c8331d34646726ea92020-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009027https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known about pattern recognition of T. gondii within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic T. gondii infection, but, like many other pattern recognition pathways, IL-33 can signal peripherally, and the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during T. gondii infection, is released locally into the cerebrospinal fluid of T. gondii-infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment and/or maintenance of blood-derived anti-parasitic immune cells, including proliferating, IFN-γ-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33 receptor-deficient astrocytes fail to mount an adequate adaptive immune response in the CNS to control parasite burden-demonstrating, genetically, that astrocytes can directly respond to IL-33 in vivo. Together, these results indicate a brain-specific mechanism by which IL-33 is released locally, and sensed locally, to engage the peripheral immune system in controlling a pathogen.Katherine M StillSamantha J BatistaCarleigh A O'BrienOyebola O OyesolaSimon P FrühLauren M WebbIgor SmirnovMichael A KovacsMaureen N CowanNikolas W HayesJeremy A ThompsonElia D Tait WojnoTajie H HarrisPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 16, Iss 10, p e1009027 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Katherine M Still Samantha J Batista Carleigh A O'Brien Oyebola O Oyesola Simon P Früh Lauren M Webb Igor Smirnov Michael A Kovacs Maureen N Cowan Nikolas W Hayes Jeremy A Thompson Elia D Tait Wojno Tajie H Harris Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
description	It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known about pattern recognition of T. gondii within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic T. gondii infection, but, like many other pattern recognition pathways, IL-33 can signal peripherally, and the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during T. gondii infection, is released locally into the cerebrospinal fluid of T. gondii-infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment and/or maintenance of blood-derived anti-parasitic immune cells, including proliferating, IFN-γ-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33 receptor-deficient astrocytes fail to mount an adequate adaptive immune response in the CNS to control parasite burden-demonstrating, genetically, that astrocytes can directly respond to IL-33 in vivo. Together, these results indicate a brain-specific mechanism by which IL-33 is released locally, and sensed locally, to engage the peripheral immune system in controlling a pathogen.
format	article
author	Katherine M Still Samantha J Batista Carleigh A O'Brien Oyebola O Oyesola Simon P Früh Lauren M Webb Igor Smirnov Michael A Kovacs Maureen N Cowan Nikolas W Hayes Jeremy A Thompson Elia D Tait Wojno Tajie H Harris
author_facet	Katherine M Still Samantha J Batista Carleigh A O'Brien Oyebola O Oyesola Simon P Früh Lauren M Webb Igor Smirnov Michael A Kovacs Maureen N Cowan Nikolas W Hayes Jeremy A Thompson Elia D Tait Wojno Tajie H Harris
author_sort	Katherine M Still
title	Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
title_short	Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
title_full	Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
title_fullStr	Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
title_full_unstemmed	Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.
title_sort	astrocytes promote a protective immune response to brain toxoplasma gondii infection via il-33-st2 signaling.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/15e74006523b4a4c8331d34646726ea9
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Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling.

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