Differential expression of viral pathogen-associated molecular pattern receptors mRNA in Egyptian chronic hepatitis C virus patients
Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hi...
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Published in | Egyptian Journal of Medical Human Genetics Vol. 22; no. 1; pp. 13 - 9 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Berlin/Heidelberg
Springer Berlin Heidelberg
26.02.2021
Springer Springer Nature B.V SpringerOpen |
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Abstract | Background
One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls.
Results
The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7.
Conclusion
The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. |
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AbstractList | Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host's innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-[alpha] to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-[alpha] in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. Results The expression levels of TLR3, TLR7, and IFN-[alpha] were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-[alpha]) compared to control group. Obviously, the expression levels of IFN-[alpha] were positively correlated with the levels of both TLR3 and TLR7. Conclusion The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-[alpha] production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. BackgroundOne possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls.ResultsThe expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7.ConclusionThe exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host's innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-[alpha] to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-[alpha] in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. The expression levels of TLR3, TLR7, and IFN-[alpha] were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-[alpha]) compared to control group. Obviously, the expression levels of IFN-[alpha] were positively correlated with the levels of both TLR3 and TLR7. The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-[alpha] production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. Results The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7. Conclusion The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. Abstract Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. Results The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7. Conclusion The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies. |
Audience | Professional Academic |
Author | Weigand, Kilian Farag, Mohamed M. S. Mohamed, Ezz Elden M. Suef, Reda A. Mansour, Mohamed T. M. |
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References_xml | – reference: PandeySKawaiTAkiraSMicrobial sensing by toll-like receptors and intracellular nucleic acid sensorsCold Spring Harb Perspect Biol20157a01624610.1101/cshperspect.a016246 – reference: MetzPReuterABenderSInterferon-stimulated genes, and their role in controlling hepatitis C. virusJ Hepatol201359133113411:CAS:528:DC%2BC3sXhsFelurnL10.1016/j.jhep.2013.07.033 – reference: LiKFoyEFerreonJCImmune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the toll-like receptor 3 adaptor protein TRIF ProcNatl Acad Sci USA2005102299229971:CAS:528:DC%2BD2MXitVSkt7g%3D10.1073/pnas.0408824102 – reference: GhonaimAzizMostafaToll-like receptor 7 expression and gene polymorphism in patients with hepatitis C and hepatocellular carcinomaEgypt J Med Microbiol2019284 – reference: JacobsBLLanglandJOWhen two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNAVirology.19962193393491:CAS:528:DyaK28XjtVSgt74%3D10.1006/viro.1996.02598638399 – reference: HiscottJNguyenTLArguelloMManipulation of the nuclear factor-kappa B pathway and the innate immune response by virusesOncogene.200625684468671:CAS:528:DC%2BD28XhtFekt7fF10.1038/sj.onc.1209941170723327100320 – reference: Dehghan-ManshadiMHadinedoushanHAmirbaigyMKRelative expression of toll-like receptors 2 and 7 mRNA in peripheral blood of patients with hepatitis CHepat Mon20151511e3042710.5812/hepatmon.30427268347884719121 – reference: HornungVRothenfusserSBritschSQuantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotidesJ Immunol2002168453145371:CAS:528:DC%2BD38Xjt12jt7k%3D10.4049/jimmunol.168.9.453111970999 – reference: ChenKHuangJLiuYSynergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein- coupled receptor, in microglial cellsJ Neuroimmunol20092131-269771:CAS:528:DC%2BD1MXps1WhsLw%3D10.1016/j.jneuroim.2009.05.018195594902761824 – reference: VersteegGAGarcia-SastreAViral tricks to grid-lock the type I interferon systemCurr Opin Microbiol2010135085161:CAS:528:DC%2BC3cXpvVaqtbw%3D10.1016/j.mib.2010.05.009 – reference: TakedaKAkiraSToll-like receptors in innate immunityInt Immunol2005171141:CAS:528:DC%2BD2cXhtVKru77P10.1093/intimm/dxh18615585605 – reference: UrbanowiczZagożdżonCiszekMModulation of the immune system in chronic hepatitis C and during antiviral interferon-free therapyArch Immunol Ther Exp201967279881:CAS:528:DC%2BC1cXit1Wiu7bF10.1007/s00005-018-0532-8Birkhauser Verlag AG – reference: AgrawalBKrishnadasDKKumarRProteins derived from hepatitis C virus modulate immune responses: targeting dendritic cellsInt Immunol20122227481:CAS:528:DC%2BC3cXms1OmsL8%3D10.1093/intimm/dxq033 – reference: EasterbrookPJGroupWGDWho to test and how to test for chronic hepatitis C infection–2016 WHO testing guidance for low-and middle-income countriesJ Hepatol2016651S46S6610.1016/j.jhep.2016.08.002 – reference: MotavafMNoorbakhshFAlavianSMDistinct toll-like receptor 3 and 7 expression in peripheral blood mononuclear cells from patients with chronic hepatitis C infectionHepat Mon2014144e1642110.5812/hepatmon.16421247488963989766 – reference: MatsumotoMKikkawaSKohaseMEstablishment of a monoclonal antibody against human toll-like receptor 3 that blocks double-stranded RNA-mediated signalingBiochem Biophys Res Commun20022935136413691:CAS:528:DC%2BD38Xks1Ghu7c%3D10.1016/S0006-291X(02)00380-712054664 – reference: HondaKTaniguchiTIRFs: master regulators of signaling by toll-like receptors and cytosolic pattern-recognition receptorsNat Rev Immunol200666446581:CAS:528:DC%2BD28Xos12gtrY%3D10.1038/nri1900 – reference: ElgharablyAGomaaAICrosseyMMHepatitis C in Egypt – past, present, and futureInt J Gen Med2017101610.2147/IJGM.S11930128053553 – reference: LiangCaoDingHepatitis C virus NS4B induces the degradation of TRIF to inhibit TLR3-mediated interferon signaling pathwayPLoS Pathog2018145e10070751:CAS:528:DC%2BC1cXhvFCmtrjM10.1371/journal.ppat.1007075297825325983870 – reference: HamdyOsmanZakariaAssociation of toll-like receptor 3 and toll-like receptor 9 single-nucleotide polymorphisms with hepatitis C virus persistence among EgyptiansArch Virol20181639243324421:CAS:528:DC%2BC1cXhtVOls7nJ10.1007/s00705-018-3893-829860675 – reference: SantoroMGRossiAAmiciCNF-kB and virus infection: who controls whomEMBO J200322255225601:CAS:528:DC%2BD3sXkt1WrtL4%3D10.1093/emboj/cdg26712773372156764 – reference: MohammedKIAdelLAAli-EldinFAExpression of toll like receptors 3 & 7 in peripheral blood from patients with chronic hepatitis C virus infection and their correlation with interferon-alphaEgypt J Immunol2013201132223888553 – reference: OrzalliMHKnipeDMCellular sensing of viral DNA and viral evasion mechanismsAnnu Rev Microbiol2014684774921:CAS:528:DC%2BC2cXhvVGrsbbO10.1146/annurev-micro-091313-103409 – reference: RayStuartCThomas“Chapter 154: Hepatitis C”. Principles and practice of infectious diseases20097PhiladelphiaChurchill LivingstoneISBN 978-0-443-06839-3 – reference: TakedaKAkiraSTLR signaling pathwaysSemin Immunol200416391:CAS:528:DC%2BD2cXntVOnsA%3D%3D10.1016/j.smim.2003.10.00314751757 – reference: BaxtLAGarza-MayersACGoldbergMBBacterial subversion of host innate immune pathwaysScience20133406977011:CAS:528:DC%2BC3sXntVGjtro%3D10.1126/science.1235771 – reference: RosadiniCVKaganJCMicrobial strategies for antagonizing toll-like-receptor signal transductionCurr Opin Immunol20153261701:CAS:528:DC%2BC2MXmtFWrsw%3D%3D10.1016/j.coi.2014.12.011 – reference: HornerSMActivation and evasion of antiviral innate immunity by hepatitis C virusJ Mol Biol2014426119812091:CAS:528:DC%2BC3sXhslOjsL%2FO10.1016/j.jmb.2013.10.032 – reference: SahaBSzaboGInnate immune cell networking in hepatitis C virus infectionJ Leukoc Biol201496.57577661:CAS:528:DC%2BC2cXitFWns7bJ10.1189/jlb.4MR0314-141R – reference: KamalSMAcute hepatitis C: a systematic reviewAm J Gastroenterol20081031283e129710.1111/j.1572-0241.2008.01825.x – reference: ChenYChenJWangHHCV-induced miR-2 contributes to evasion of host immune system by targeting MyD88 and IRAK1PLoS Pathog20139e10032481:CAS:528:DC%2BC3sXntlCrurY%3D10.1371/journal.ppat.1003248 – reference: SalemMIbrahimEMEl-BateHEx vivo generation and maturation of dendritic cells from peripheral blood mononuclear cells of patients with chronic HCV or hepatocellular carcinoma using toll-like receptor 3 ligand poly(I:C)Int J Cancer Biomed Res201821111810.21608/jcbr.2019.34740 |
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One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its... Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host's innate immune surveillance is modification of its... One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host's innate immune surveillance is modification of its pathogen-associated... BackgroundOne possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its... Abstract Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its... |
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SubjectTerms | Analysis B cells Chemokines Genotypes Health aspects Hepatitis C Hepatitis C virus IFN-α transcription Immune response Immunosurveillance Inflammation Innate immunity Interferon Medical research Medicine Medicine & Public Health Medicine, Experimental Messenger RNA mRNA Pathogens Peripheral blood TLR3 and TLR7 signaling TLR3 protein TLR7 protein Toll-like receptors α-Interferon |
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Title | Differential expression of viral pathogen-associated molecular pattern receptors mRNA in Egyptian chronic hepatitis C virus patients |
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