Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System 英文参考文献.docVIP

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Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System 英文参考文献.doc

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Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System 英文参考文献

EffectoftheNovelInfluenzaA(H1N1)Virusinthe HumanImmuneSystem EvangelosJ.Giamarellos-Bourboulis*,MariaRaftogiannis,AnastasiaAntonopoulou,FotiniBaziaka, PantelisKoutoukas,AthinaSavva,TheodoraKanni,MariannaGeorgitsi,AikateriniPistiki,Thomas Tsaganos,NikolaosPelekanos,SofiaAthanassia,LabriniGalani,EfthymiaGiannitsioti,DimitraKavatha, FloraKontopidou,MariaMouktaroudi,GaryfalliaPoulakou,VissariaSakka,PeriklisPanagopoulos, AntoniosPapadopoulos,KyriakiKanellakopoulou,HelenGiamarellou 4thDepartmentofInternalMedicine,UniversityofAthens,MedicalSchool,Greece,Athens,Greece Abstract Background:ThepandemicbythenovelH1N1virushascreatedtheneedtostudyanyprobableeffectsofthatinfectionin theimmunesystemofthehost. Methodology/PrincipalFindings:Bloodwassampledwithinthefirsttwodaysofthepresentationofsignsofinfectionfrom 10healthyvolunteers;from18casesofflu-likesyndrome;andfrom31casesofinfectionbyH1N1confirmedbyreverseRT- PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral bloodmononuclear cells (PBMCs) were isolated from patients and stimulatedwithvariousbacterialstimuli.Concentrationsoftumournecrosisfactor-alpha,interleukin(IL)-1beta,IL-6,IL-18, interferon(FN)-alphaandofIFN-gammawereestimatedinsupernatantsbyanenzymeimmunoassay.InfectionbyH1N1 wasaccompaniedbyanincreaseofmonocytes.PBMCsofpatientsevokedstrongcytokineproductionafterstimulationwith mostofbacterialstimuli.Defectivecytokineresponseswereshowninresponsetostimulationwithphytohemagglutinand withheat-killedStreptococcuspneumoniae.AdaptiveimmuneresponsesofH1N1-infectedpatientswerecharacterizedby decreasesofCD4-lymphocytesandofB-lymphocytesandbyincreaseofT-regulatorylymphocytes(Tregs). Conclusions/Significance:InfectionbytheH1N1virusisaccompaniedbyacharacteristicimpairmentoftheinnateimmune responsescharacterizedbydefectivecytokineresponsestoS.pneumoniae.Alterationsoftheadaptiveimmuneresponses arepredominatedbyincreaseof