TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection

Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G a...

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Veröffentlicht in:PloS one 2011-10, Vol.6 (10), p.e26235-e26235
Hauptverfasser: Wang, Chiou-Huey, Eng, Hock-Liew, Lin, Kuei-Hsiang, Chang, Cheng-Hsien, Hsieh, Chi-An, Lin, Yen-Li, Lin, Tsun-Mei
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container_issue 10
container_start_page e26235
container_title PloS one
container_volume 6
creator Wang, Chiou-Huey
Eng, Hock-Liew
Lin, Kuei-Hsiang
Chang, Cheng-Hsien
Hsieh, Chi-An
Lin, Yen-Li
Lin, Tsun-Mei
description Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection.
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We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026235</identifier><identifier>PMID: 22022576</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive control ; Adaptive immunity ; Antigens ; B cells ; Biology ; Case-Control Studies ; CD14 antigen ; Chlamydia ; Chromosomes ; Control systems ; Cytokines ; Cytokines - biosynthesis ; Dendritic cells ; Development and progression ; Disease susceptibility ; Ethnic Groups - genetics ; Female ; Females ; Gene expression ; Gene Expression Regulation ; Gene Frequency - genetics ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genotypes ; Haplotypes ; Haplotypes - genetics ; Health aspects ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - genetics ; Hospitals ; Humans ; Immune response ; Immune system ; Immunity ; Infection ; Infections ; Inflammation ; Innate immunity ; Interferon ; Intracellular Space - metabolism ; Male ; Males ; Medical laboratories ; Medicine ; Middle Aged ; mRNA ; Polymorphism, Single Nucleotide - genetics ; Proteins ; Receptors ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Studies ; TLR7 protein ; Toll-Like Receptor 7 - agonists ; Toll-Like Receptor 7 - genetics ; Toll-Like Receptor 7 - metabolism ; Toll-Like Receptor 8 - agonists ; Toll-Like Receptor 8 - genetics ; Toll-Like Receptor 8 - metabolism ; Toll-like receptors ; Viruses</subject><ispartof>PloS one, 2011-10, Vol.6 (10), p.e26235-e26235</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Wang et al. 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We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. 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biosynthesis</topic><topic>Dendritic cells</topic><topic>Development and progression</topic><topic>Disease susceptibility</topic><topic>Ethnic Groups - genetics</topic><topic>Female</topic><topic>Females</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene Frequency - genetics</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotypes</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Health aspects</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - genetics</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Infection</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>Interferon</topic><topic>Intracellular Space - metabolism</topic><topic>Male</topic><topic>Males</topic><topic>Medical laboratories</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>Polymorphism, Single Nucleotide - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Chiou-Huey</au><au>Eng, Hock-Liew</au><au>Lin, Kuei-Hsiang</au><au>Chang, Cheng-Hsien</au><au>Hsieh, Chi-An</au><au>Lin, Yen-Li</au><au>Lin, Tsun-Mei</au><au>Sambhara, Suryaprakash</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-10-13</date><risdate>2011</risdate><volume>6</volume><issue>10</issue><spage>e26235</spage><epage>e26235</epage><pages>e26235-e26235</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22022576</pmid><doi>10.1371/journal.pone.0026235</doi><tpages>e26235</tpages><oa>free_for_read</oa></addata></record>
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subjects Adaptive control
Adaptive immunity
Antigens
B cells
Biology
Case-Control Studies
CD14 antigen
Chlamydia
Chromosomes
Control systems
Cytokines
Cytokines - biosynthesis
Dendritic cells
Development and progression
Disease susceptibility
Ethnic Groups - genetics
Female
Females
Gene expression
Gene Expression Regulation
Gene Frequency - genetics
Genes
Genetic aspects
Genetic Predisposition to Disease
Genotypes
Haplotypes
Haplotypes - genetics
Health aspects
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - genetics
Hospitals
Humans
Immune response
Immune system
Immunity
Infection
Infections
Inflammation
Innate immunity
Interferon
Intracellular Space - metabolism
Male
Males
Medical laboratories
Medicine
Middle Aged
mRNA
Polymorphism, Single Nucleotide - genetics
Proteins
Receptors
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Studies
TLR7 protein
Toll-Like Receptor 7 - agonists
Toll-Like Receptor 7 - genetics
Toll-Like Receptor 7 - metabolism
Toll-Like Receptor 8 - agonists
Toll-Like Receptor 8 - genetics
Toll-Like Receptor 8 - metabolism
Toll-like receptors
Viruses
title TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T02%3A09%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TLR7%20and%20TLR8%20gene%20variations%20and%20susceptibility%20to%20hepatitis%20C%20virus%20infection&rft.jtitle=PloS%20one&rft.au=Wang,%20Chiou-Huey&rft.date=2011-10-13&rft.volume=6&rft.issue=10&rft.spage=e26235&rft.epage=e26235&rft.pages=e26235-e26235&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0026235&rft_dat=%3Cgale_plos_%3EA476868688%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1309830436&rft_id=info:pmid/22022576&rft_galeid=A476868688&rft_doaj_id=oai_doaj_org_article_9c50e30166044796bc00f9e64ea1b7f3&rfr_iscdi=true