Pleiotropic effects of Blastocystis spp. Subtypes 4 and 7 on ligand-specific toll-like receptor signaling and NF-κB activation in a human monocyte cell line
Blastocystis spp. is a common enteric stramenopile parasite that colonizes the colon of hosts of a diverse array of species, including humans. It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal...
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| description | Blastocystis spp. is a common enteric stramenopile parasite that colonizes the colon of hosts of a diverse array of species, including humans. It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal epithelial surfaces, including the intestinal epithelium, are increasingly recognized to perform a vital surveillance role in the context of innate immunity, through the expression of pathogen recognition receptors, such as Toll-like receptors (TLRs). In this study, we use the human TLR reporter monocytic cell line, THP1-Blue, which expresses all human TLRs, to investigate effects of Blastocystis on TLR activation, more specifically the activation of TLR-2, -4 and -5. We have observed that live Blastocystis spp. parasites and whole cell lysate (WCL) alone do not activate TLRs in THP1-Blue. Live ST4-WR1 parasites inhibited LPS-mediated NF-κB activation in THP1-Blue. In contrast, ST7-B WCL and ST4-WR1 WCL induced pleiotropic modulation of ligand-specific TLR-2 and TLR-4 activation, with no significant effects on flagellin-mediated TLR-5 activation. Real time-qPCR analysis on SEAP reporter gene confirmed the augmenting effect of ST7-B on LPS-mediated NF-κB activation in THP1-Blue. Taken together, this is the first study to characterize interactions between Blastocystis spp. and host TLR activation using an in vitro reporter model. |
| doi_str_mv | 10.1371/journal.pone.0089036 |
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It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal epithelial surfaces, including the intestinal epithelium, are increasingly recognized to perform a vital surveillance role in the context of innate immunity, through the expression of pathogen recognition receptors, such as Toll-like receptors (TLRs). In this study, we use the human TLR reporter monocytic cell line, THP1-Blue, which expresses all human TLRs, to investigate effects of Blastocystis on TLR activation, more specifically the activation of TLR-2, -4 and -5. We have observed that live Blastocystis spp. parasites and whole cell lysate (WCL) alone do not activate TLRs in THP1-Blue. Live ST4-WR1 parasites inhibited LPS-mediated NF-κB activation in THP1-Blue. In contrast, ST7-B WCL and ST4-WR1 WCL induced pleiotropic modulation of ligand-specific TLR-2 and TLR-4 activation, with no significant effects on flagellin-mediated TLR-5 activation. Real time-qPCR analysis on SEAP reporter gene confirmed the augmenting effect of ST7-B on LPS-mediated NF-κB activation in THP1-Blue. Taken together, this is the first study to characterize interactions between Blastocystis spp. and host TLR activation using an in vitro reporter model.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0089036</identifier><identifier>PMID: 24551212</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology ; Blastocystis - drug effects ; Blastocystis - physiology ; Cell activation ; Cell Extracts ; Cell Line ; Chemokines ; Colon ; Cytokines ; Epithelial cells ; Epithelium ; Experiments ; Flagellin ; Flagellin - pharmacology ; Food allergies ; Genetic diversity ; Homeostasis ; Hot Temperature ; Humans ; Immune system ; Immunity ; Immunology ; Inflammation ; Innate immunity ; Intestine ; Irritable bowel syndrome ; Kinases ; Laboratories ; Ligands ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Medicine ; Monocytes ; Monocytes - drug effects ; Monocytes - metabolism ; Monocytes - parasitology ; Mucosa ; NF-kappa B - metabolism ; NF-κB protein ; Parasites ; Parasites - drug effects ; Parasitology ; Proteins ; Receptors ; Reporter gene ; Rodents ; Signal Transduction - drug effects ; Signaling ; Small intestine ; Studies ; TLR2 protein ; Toll-like receptors ; Toll-Like Receptors - metabolism ; Zymosan - pharmacology</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e89036</ispartof><rights>2014 Teo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Teo et al 2014 Teo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-75c606ee1f2ef0c9efc0f3f12db30ea7bc93f616e8bbf34496c3ffcc2a06e0193</citedby><cites>FETCH-LOGICAL-c526t-75c606ee1f2ef0c9efc0f3f12db30ea7bc93f616e8bbf34496c3ffcc2a06e0193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925187/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925187/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24551212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wang, Tianyi</contributor><creatorcontrib>Teo, Joshua D W</creatorcontrib><creatorcontrib>Macary, Paul A</creatorcontrib><creatorcontrib>Tan, Kevin S W</creatorcontrib><title>Pleiotropic effects of Blastocystis spp. Subtypes 4 and 7 on ligand-specific toll-like receptor signaling and NF-κB activation in a human monocyte cell line</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Blastocystis spp. is a common enteric stramenopile parasite that colonizes the colon of hosts of a diverse array of species, including humans. It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal epithelial surfaces, including the intestinal epithelium, are increasingly recognized to perform a vital surveillance role in the context of innate immunity, through the expression of pathogen recognition receptors, such as Toll-like receptors (TLRs). In this study, we use the human TLR reporter monocytic cell line, THP1-Blue, which expresses all human TLRs, to investigate effects of Blastocystis on TLR activation, more specifically the activation of TLR-2, -4 and -5. We have observed that live Blastocystis spp. parasites and whole cell lysate (WCL) alone do not activate TLRs in THP1-Blue. Live ST4-WR1 parasites inhibited LPS-mediated NF-κB activation in THP1-Blue. In contrast, ST7-B WCL and ST4-WR1 WCL induced pleiotropic modulation of ligand-specific TLR-2 and TLR-4 activation, with no significant effects on flagellin-mediated TLR-5 activation. Real time-qPCR analysis on SEAP reporter gene confirmed the augmenting effect of ST7-B on LPS-mediated NF-κB activation in THP1-Blue. Taken together, this is the first study to characterize interactions between Blastocystis spp. and host TLR activation using an in vitro reporter model.</description><subject>Animals</subject><subject>Biology</subject><subject>Blastocystis - drug effects</subject><subject>Blastocystis - physiology</subject><subject>Cell activation</subject><subject>Cell Extracts</subject><subject>Cell Line</subject><subject>Chemokines</subject><subject>Colon</subject><subject>Cytokines</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Experiments</subject><subject>Flagellin</subject><subject>Flagellin - pharmacology</subject><subject>Food allergies</subject><subject>Genetic diversity</subject><subject>Homeostasis</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Intestine</subject><subject>Irritable bowel syndrome</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - 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drug effects</topic><topic>Blastocystis - physiology</topic><topic>Cell activation</topic><topic>Cell Extracts</topic><topic>Cell Line</topic><topic>Chemokines</topic><topic>Colon</topic><topic>Cytokines</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Experiments</topic><topic>Flagellin</topic><topic>Flagellin - pharmacology</topic><topic>Food allergies</topic><topic>Genetic diversity</topic><topic>Homeostasis</topic><topic>Hot Temperature</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>Intestine</topic><topic>Irritable bowel syndrome</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Ligands</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medicine</topic><topic>Monocytes</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - parasitology</topic><topic>Mucosa</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Parasites</topic><topic>Parasites - drug effects</topic><topic>Parasitology</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Reporter gene</topic><topic>Rodents</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Small intestine</topic><topic>Studies</topic><topic>TLR2 protein</topic><topic>Toll-like receptors</topic><topic>Toll-Like Receptors - metabolism</topic><topic>Zymosan - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teo, Joshua D W</creatorcontrib><creatorcontrib>Macary, Paul A</creatorcontrib><creatorcontrib>Tan, Kevin S W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal epithelial surfaces, including the intestinal epithelium, are increasingly recognized to perform a vital surveillance role in the context of innate immunity, through the expression of pathogen recognition receptors, such as Toll-like receptors (TLRs). In this study, we use the human TLR reporter monocytic cell line, THP1-Blue, which expresses all human TLRs, to investigate effects of Blastocystis on TLR activation, more specifically the activation of TLR-2, -4 and -5. We have observed that live Blastocystis spp. parasites and whole cell lysate (WCL) alone do not activate TLRs in THP1-Blue. Live ST4-WR1 parasites inhibited LPS-mediated NF-κB activation in THP1-Blue. In contrast, ST7-B WCL and ST4-WR1 WCL induced pleiotropic modulation of ligand-specific TLR-2 and TLR-4 activation, with no significant effects on flagellin-mediated TLR-5 activation. Real time-qPCR analysis on SEAP reporter gene confirmed the augmenting effect of ST7-B on LPS-mediated NF-κB activation in THP1-Blue. Taken together, this is the first study to characterize interactions between Blastocystis spp. and host TLR activation using an in vitro reporter model.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24551212</pmid><doi>10.1371/journal.pone.0089036</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biology Blastocystis - drug effects Blastocystis - physiology Cell activation Cell Extracts Cell Line Chemokines Colon Cytokines Epithelial cells Epithelium Experiments Flagellin Flagellin - pharmacology Food allergies Genetic diversity Homeostasis Hot Temperature Humans Immune system Immunity Immunology Inflammation Innate immunity Intestine Irritable bowel syndrome Kinases Laboratories Ligands Lipopolysaccharides Lipopolysaccharides - pharmacology Medicine Monocytes Monocytes - drug effects Monocytes - metabolism Monocytes - parasitology Mucosa NF-kappa B - metabolism NF-κB protein Parasites Parasites - drug effects Parasitology Proteins Receptors Reporter gene Rodents Signal Transduction - drug effects Signaling Small intestine Studies TLR2 protein Toll-like receptors Toll-Like Receptors - metabolism Zymosan - pharmacology |
| title | Pleiotropic effects of Blastocystis spp. Subtypes 4 and 7 on ligand-specific toll-like receptor signaling and NF-κB activation in a human monocyte cell line |
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