SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection

Abstract Central nervous system (CNS) injury and infection can result in profound tissue remodeling in the brain, the mechanism and purpose of which is poorly understood. Infection with the protozoan parasite Toxoplasma gondii causes chronic infection and inflammation in the brain parenchyma. Contro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kathryn E. McGovern, J. Philip Nance, Clément N. David, Reed E. S. Harrison, Shahani Noor, Danielle Worth, Tyler A. Landrith, Andre Obenaus, Monica J. Carson, Dimitrios Morikis, Emma H. Wilson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37ea326e19414df5ac396cbe47c69847
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:37ea326e19414df5ac396cbe47c69847
record_format	dspace
spelling	oai:doaj.org-article:37ea326e19414df5ac396cbe47c698472021-12-02T13:34:58ZSPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection10.1038/s41598-021-83952-02045-2322https://doaj.org/article/37ea326e19414df5ac396cbe47c698472021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83952-0https://doaj.org/toc/2045-2322Abstract Central nervous system (CNS) injury and infection can result in profound tissue remodeling in the brain, the mechanism and purpose of which is poorly understood. Infection with the protozoan parasite Toxoplasma gondii causes chronic infection and inflammation in the brain parenchyma. Control of parasite replication requires the continuous presence of IFNγ-producing T cells to keep T. gondii in its slowly replicating cyst form. During infection, a network of extracellular matrix fibers, revealed using multiphoton microscopy, forms in the brain. The origin and composition of these structures are unknown but the fibers have been observed to act as a substrate for migrating T cells. In this study, we show a critical regulator of extracellular matrix (ECM) remodeling, Secreted Protein, Acidic, Rich in Cysteine (SPARC), is upregulated in the brain during the early phases of infection in the frontal cortex. In the absence of SPARC, a reduced and disordered fibrous network, increased parasite burden, and reduced antigen-specific T cell entry into the brain points to a role for SPARC in T cell recruitment to and migration within the brain. We also report SPARC can directly bind to CCR7 ligands CCL19 and CCL21 but not CXCL10, and enhance migration toward a chemokine gradient. Measurement of T cell behavior points to tissue remodeling being important for access of immune cells to the brain and facilitating cellular locomotion. Together, these data identify SPARC as an important regulatory component of immune cell trafficking and access to the inflamed CNS.Kathryn E. McGovernJ. Philip NanceClément N. DavidReed E. S. HarrisonShahani NoorDanielle WorthTyler A. LandrithAndre ObenausMonica J. CarsonDimitrios MorikisEmma H. WilsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kathryn E. McGovern J. Philip Nance Clément N. David Reed E. S. Harrison Shahani Noor Danielle Worth Tyler A. Landrith Andre Obenaus Monica J. Carson Dimitrios Morikis Emma H. Wilson SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
description	Abstract Central nervous system (CNS) injury and infection can result in profound tissue remodeling in the brain, the mechanism and purpose of which is poorly understood. Infection with the protozoan parasite Toxoplasma gondii causes chronic infection and inflammation in the brain parenchyma. Control of parasite replication requires the continuous presence of IFNγ-producing T cells to keep T. gondii in its slowly replicating cyst form. During infection, a network of extracellular matrix fibers, revealed using multiphoton microscopy, forms in the brain. The origin and composition of these structures are unknown but the fibers have been observed to act as a substrate for migrating T cells. In this study, we show a critical regulator of extracellular matrix (ECM) remodeling, Secreted Protein, Acidic, Rich in Cysteine (SPARC), is upregulated in the brain during the early phases of infection in the frontal cortex. In the absence of SPARC, a reduced and disordered fibrous network, increased parasite burden, and reduced antigen-specific T cell entry into the brain points to a role for SPARC in T cell recruitment to and migration within the brain. We also report SPARC can directly bind to CCR7 ligands CCL19 and CCL21 but not CXCL10, and enhance migration toward a chemokine gradient. Measurement of T cell behavior points to tissue remodeling being important for access of immune cells to the brain and facilitating cellular locomotion. Together, these data identify SPARC as an important regulatory component of immune cell trafficking and access to the inflamed CNS.
format	article
author	Kathryn E. McGovern J. Philip Nance Clément N. David Reed E. S. Harrison Shahani Noor Danielle Worth Tyler A. Landrith Andre Obenaus Monica J. Carson Dimitrios Morikis Emma H. Wilson
author_facet	Kathryn E. McGovern J. Philip Nance Clément N. David Reed E. S. Harrison Shahani Noor Danielle Worth Tyler A. Landrith Andre Obenaus Monica J. Carson Dimitrios Morikis Emma H. Wilson
author_sort	Kathryn E. McGovern
title	SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
title_short	SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
title_full	SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
title_fullStr	SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
title_full_unstemmed	SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
title_sort	sparc coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific t cells in the brain following infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/37ea326e19414df5ac396cbe47c69847
work_keys_str_mv	AT kathrynemcgovern sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT jphilipnance sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT clementndavid sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT reedesharrison sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT shahaninoor sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT danielleworth sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT tyleralandrith sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT andreobenaus sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT monicajcarson sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT dimitriosmorikis sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection AT emmahwilson sparccoordinatesextracellularmatrixremodelingandefficientrecruitmenttoandmigrationofantigenspecifictcellsinthebrainfollowinginfection
_version_	1718392727526178816

SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection

Ejemplares similares