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Multidrug-resistant Mycobacterium tuberculosis infected macrophages 2,4 regulatory role of Toll-like receptor

Author: RenWeiCong
Tutor: LiChuanYou
School: Beijing Tuberculosis and Thoracic Tumor Research Institute
Course: Immunology
Keywords: Toll-like receptor Mycobacterium tuberculosis MDR THP-1
CLC: R392
Type: Master's thesis
Year: 2009
Downloads: 96
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Abstract


Toll-like receptors (TLRs) , a family of pattern recognition receptors expressed on mammalian cell surface , are evolutionarily conserved to recognize pathogen-associated molecular patterns(PAMPs). The activation of TLRs not only initiates innate immunity, but also regulates antigen-specific acquired immunity, and thus contacts innate and adaptive immunity.This study showed that TLRs were key elements which induced host cell recognized Mycobacterium tuberculosis(MTB)and anti-TB immune response. TLR2 and TLR4 were the main anti-tuberculosis immune response ,TLRs have been engaged in the host immune response through the identification of MTB and MTB components. Research on TLRs contributes to a clarify the pathogenesis of TB and provides the brand-new strategy for its treatment.THP-1 cells were respectively infected with MDR strains and drug-sensitive(DC) m. tuberculosis strains, Reverse transcription Real-time PCR was used to detect the changes of TLR2, TLR4, P50 gene expression and IL-12, IL-4, IFN-γgene expression in mRNA level at different stage after infection,Flow Cytometry was used to detect the changes of TLR2, TLR4 gene expression.Reverse transcription Real-time PCR was used to detect the changes of TLR2, TLR4, P50 gene expression after the THP-1 cells were stimulated by different cytokines. The results showed that the regulation of TLR2、TLR4 gene expression was different between MDR-TB strains and drug-sensitive m. tuberculosis strains,The MDR-TB strains stimulated less expression of TLR2 and TLR4 than the drug-sensitive m. tuberculosis strains and that the cytokines expression is different after THP-1 cells were infected by different MTB , The MDR-TB strain stimulated less expression of cytokines IL-12、IFN-γthan the drug-sensitive m. tuberculosis strains and that cytokines also can regulate TLR2、TLR4 gene expression , IFN-γincresed the TLR2、TLR4 gene expression and IL-4 made TLR2 gene expression go down.This study suggested that Toll like receptor,as a family of pattern recognition receptors expressed on cell surface ,could recognize MTB and MTB components and induced anti-TB immune response by triggering anti-microbial innate immune responses .Different extent drug-resistance of the same genotype mycobacteria, MDR-TB strains and drug-sensitive m. tuberculosis strains, might stimulate the expression of the TLR2 and TLR4 differently and induce the different cytokines which regulate TLR gene expression.The immune response is regulated more timely, accurate, precise through the feedback mechanism by the interaction between TLR and cytokines.

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