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...
Autores principales: | , , , , , |
---|---|
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 |