Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived Macrophages 英文参考文献.docVIP

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Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived Macrophages 英文参考文献.doc

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Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived Macrophages 英文参考文献

ModernLineagesofMycobacteriumtuberculosisExhibit Lineage-SpecificPatternsofGrowthandCytokine InductioninHumanMonocyte-DerivedMacrophages RajeshSarkar1,LauraLenders1,KatalinA.Wilkinson3,5,RobertJ.Wilkinson3,4,5,MarkP.Nicol1,2,3 * 1DivisionofMedicalMicrobiology,UniversityofCapeTown,CapeTown,SouthAfrica,2NationalHealthLaboratoryServices,GrooteSchuurHospital,CapeTown,South Africa, 3Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 4DivisionofMedicine,ImperialCollegeLondon,London,UnitedKingdom,5MRCNationalInstituteforMedicalResearch,MillHill,London,UnitedKingdom Abstract Background:StrainsofMycobacteriumtuberculosisvaryinvirulence.StrainsthathavecausedoutbreaksintheUnitedStates andUnitedKingdomhavebeenshowntosubverttheinnateimmuneresponseasapotentialimmuneevasionmechanism. Thereis,however,littleinformationavailableastowhetherthesepatternsofimmunesubversionarefeaturesofindividual strainsorcharacteristicofbroadclonallineagesofM.tuberculosis. Methods:Strainsfromtwomajormodernlineages(lineage2[East-Asian]andlineage4[Euro-American])circulatinginthe WesternCapeinSouthAfricaaswellasacomparatormodernlineage(lineage3[CAS/Delhi])wereidentified.Weassessed twovirulenceassociatedcharacteristics: mycobacterialgrowth(inliquidbroth andmonocytederivedmacrophages)and earlypro-inflammatorycytokineinduction. Results:Inliquidculture,Lineage4strainsgrewmorerapidlyandreachedhigherplateaulevelsthanotherstrains(lineage4 vs.lineage2p=0.0024;lineage4vs.lineage3p=0.0005).Lineage3strainswerecharacterizedbylowandearlyplateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p,0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strainsinducedthelowestlevelsofpro-inflammatoryTNFandIL-12p40ascomparedtootherlineages(lineage2:median TNF 362pg/ml, IL-12p40 91pg/ml; li