Presence of RD149 Deletions in M. tuberculosis Central Asian Strain1 Isolates Affect Growth and TNFα Induction in THP-1 Monocytes 英文参考文献.docVIP

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Presence of RD149 Deletions in M. tuberculosis Central Asian Strain1 Isolates Affect Growth and TNFα Induction in THP-1 Monocytes 英文参考文献.doc

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Presence of RD149 Deletions in M. tuberculosis Central Asian Strain1 Isolates Affect Growth and TNFα Induction in THP-1 Monocytes 英文参考文献

PresenceofRD149DeletionsinM.tuberculosisCentral AsianStrain1IsolatesAffectGrowthandTNFaInduction inTHP-1Monocytes AkbarKanji,ZahraHasan,MehnazTanveer,RaunaqMahboob,SanaJafri,RuminaHasan* DepartmentofPathologyandMicrobiology,AgaKhanUniversity,Karachi,Pakistan Abstract Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis genogroup in South Asia. CAS1 strains carry deletionsinRD149andRD152regions.Significanceofthesedeletionsisasyetunknown.WecomparedCAS1strainswith RD149andconcurrentRD149-RD152deletionswithCAS1strainswithoutdeletionsandwiththelaboratoryreferencestrain, M.tuberculosisH37RvforgrowthandforinductionofTNFa,IL6,CCL2andIL10inTHP-1cells.GrowthofCAS1strainswith deletionswasslowerinbroth(RD149;p=0.024andRD149-RD152;p=0.025)thanthatofstrainswithoutdeletions.CAS1 strainswithRD149deletionstrainsfurthershowedreducedintracellulargrowth(p=0.013)inTHP-1cellsascomparedwith strains without deletions, and also as compared with H37Rv (p=0.007) and with CAS1 RD149-RD152 deletion strains (p=0.029).AllCAS1strainsinducedhigherlevelsofTNFaandIL10secretioninTHP-1cellsthanH37Rv.Additionally,CAS1 strainswithRD149deletionsinducedmoreTNFasecretionthanthosewithoutdeletions(p=0.013).CAS1RD149deletion strainsfromextrapulmonarysourcesshowedmorerapidgrowthandinducedlowerlevelsofTNFaandIL6secretioninTHP- 1cellsthanisolatesfrompulmonarysources.ThisdatasuggeststhatpresenceofRD149reducesgrowthandincreasesthe inductionofTNFainhostcellsbyCAS1strains.Differencesobservedforextrapulmonarystrainsmayindicateanadaptation which increases potential for dissemination and tropism outside the lung. Overall, we hypothesise that RD149 deletions generate genetic diversity within strains and impact interactions of CAS1 strains with host cells with important clinical consequences. Citation:KanjiA,HasanZ,TanveerM,MahboobR,JafriS,etal.(2011)PresenceofRD149DeletionsinM.tuberculosisCentralAsianStrain1IsolatesAffectGrowth andTNFaInductioninTHP-1Monocytes.PLoSONE6(8):e24178.doi:10.1371/journal