Cargando…

Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection

BACKGROUND: Toxoplasma gondii is capable of persisting in the brain, although it is efficiently eliminated by cellular immune responses in most other sites. While Toll-like receptor 2 (TLR2) reportedly plays important roles in protective immunity against the parasite, the relationship between neurol...

Descripción completa

Detalles Bibliográficos
Autores principales: Umeda, Kousuke, Tanaka, Sachi, Ihara, Fumiaki, Yamagishi, Junya, Suzuki, Yutaka, Nishikawa, Yoshifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685635/
https://www.ncbi.nlm.nih.gov/pubmed/29136637
http://dx.doi.org/10.1371/journal.pone.0187703
_version_ 1783278659247800320
author Umeda, Kousuke
Tanaka, Sachi
Ihara, Fumiaki
Yamagishi, Junya
Suzuki, Yutaka
Nishikawa, Yoshifumi
author_facet Umeda, Kousuke
Tanaka, Sachi
Ihara, Fumiaki
Yamagishi, Junya
Suzuki, Yutaka
Nishikawa, Yoshifumi
author_sort Umeda, Kousuke
collection PubMed
description BACKGROUND: Toxoplasma gondii is capable of persisting in the brain, although it is efficiently eliminated by cellular immune responses in most other sites. While Toll-like receptor 2 (TLR2) reportedly plays important roles in protective immunity against the parasite, the relationship between neurological disorders induced by T. gondii infection and TLR2 function in the brain remains controversial with many unknowns. In this study, primary cultured astrocytes, microglia, neurons, and peritoneal macrophages obtained from wild-type and TLR2-deficient mice were exposed to T. gondii tachyzoites. To characterize TLR2-dependent functional pathways activated in response to T. gondii infection, gene expression of different cell types was profiled by RNA sequencing. RESULTS: During T. gondii infection, a total of 611, 777, 385, and 1105 genes were upregulated in astrocytes, microglia, neurons, and macrophages, respectively, while 163, 1207, 158, and 1274 genes were downregulated, respectively, in a TLR2-dependent manner. Overrepresented Gene Ontology (GO) terms for TLR2-dependently upregulated genes were associated with immune and stress responses in astrocytes, immune responses and developmental processes in microglia, metabolic processes and immune responses in neurons, and metabolic processes and gene expression in macrophages. Overrepresented GO terms for downregulated genes included ion transport and behavior in astrocytes, cell cycle and cell division in microglia, metabolic processes in neurons, and response to stimulus, signaling and cell motility in macrophages. CONCLUSIONS: To our knowledge, this is the first transcriptomic study of TLR2 function across different cell types during T. gondii infection. Results of RNA-sequencing demonstrated roles for TLR2 varied by cell type during T. gondii infection. Our findings facilitate understanding of the detailed relationship between TLR2 and T. gondii infection, and elucidate mechanisms underlying neurological changes during infection.
format Online
Article
Text
id pubmed-5685635
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-56856352017-11-30 Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection Umeda, Kousuke Tanaka, Sachi Ihara, Fumiaki Yamagishi, Junya Suzuki, Yutaka Nishikawa, Yoshifumi PLoS One Research Article BACKGROUND: Toxoplasma gondii is capable of persisting in the brain, although it is efficiently eliminated by cellular immune responses in most other sites. While Toll-like receptor 2 (TLR2) reportedly plays important roles in protective immunity against the parasite, the relationship between neurological disorders induced by T. gondii infection and TLR2 function in the brain remains controversial with many unknowns. In this study, primary cultured astrocytes, microglia, neurons, and peritoneal macrophages obtained from wild-type and TLR2-deficient mice were exposed to T. gondii tachyzoites. To characterize TLR2-dependent functional pathways activated in response to T. gondii infection, gene expression of different cell types was profiled by RNA sequencing. RESULTS: During T. gondii infection, a total of 611, 777, 385, and 1105 genes were upregulated in astrocytes, microglia, neurons, and macrophages, respectively, while 163, 1207, 158, and 1274 genes were downregulated, respectively, in a TLR2-dependent manner. Overrepresented Gene Ontology (GO) terms for TLR2-dependently upregulated genes were associated with immune and stress responses in astrocytes, immune responses and developmental processes in microglia, metabolic processes and immune responses in neurons, and metabolic processes and gene expression in macrophages. Overrepresented GO terms for downregulated genes included ion transport and behavior in astrocytes, cell cycle and cell division in microglia, metabolic processes in neurons, and response to stimulus, signaling and cell motility in macrophages. CONCLUSIONS: To our knowledge, this is the first transcriptomic study of TLR2 function across different cell types during T. gondii infection. Results of RNA-sequencing demonstrated roles for TLR2 varied by cell type during T. gondii infection. Our findings facilitate understanding of the detailed relationship between TLR2 and T. gondii infection, and elucidate mechanisms underlying neurological changes during infection. Public Library of Science 2017-11-14 /pmc/articles/PMC5685635/ /pubmed/29136637 http://dx.doi.org/10.1371/journal.pone.0187703 Text en © 2017 Umeda et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Umeda, Kousuke
Tanaka, Sachi
Ihara, Fumiaki
Yamagishi, Junya
Suzuki, Yutaka
Nishikawa, Yoshifumi
Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title_full Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title_fullStr Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title_full_unstemmed Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title_short Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection
title_sort transcriptional profiling of toll-like receptor 2-deficient primary murine brain cells during toxoplasma gondii infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685635/
https://www.ncbi.nlm.nih.gov/pubmed/29136637
http://dx.doi.org/10.1371/journal.pone.0187703
work_keys_str_mv AT umedakousuke transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection
AT tanakasachi transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection
AT iharafumiaki transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection
AT yamagishijunya transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection
AT suzukiyutaka transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection
AT nishikawayoshifumi transcriptionalprofilingoftolllikereceptor2deficientprimarymurinebraincellsduringtoxoplasmagondiiinfection