title: Preliminary study on the virulence of XDR-TB: low virulence owing to less cytokine expression through the TLR 2 and TLR4 pathways in BLAB/C mice.
abstract: Extensively drug-resistant tuberculosis (XDR-TB) imposes a new threat to the world. In this study, XDR-TB and drug-sensitive TB (DS-TB) strains with similar genotypes were investigated. The results showed that BLAB/C mice infected with XDR-TB had reduced Toll-like receptor (TLR) 2 and TLR4 expression in lung tissues than DS-TB mice at 2 weeks post-infection. Mice infected with XDR-TB showed lower levels of TNF-α, IFN-γ, IL-4 and IL-10 in the sera than those infected with DS-TB. Moreover, mice infected with XDR-TB survived longer period and had less severe alveolar damage and smaller granulomas than those infected with DS-TB. These results were further confirmed in THP-1 cells. Using the flow cytometry and qRT-PCR methods, we found that XDR-TB stimulated lower TLR2 and TLR4 expression. Based on the above results, we cautiously inferred that low virulence of XDR-TB owed to the less cytokine expression through the TLR 2 and 4 pathways. The effect of XDR-TB and DS-TB can be further tested in TLR2 or TLR4 knock-out mice and TLRs-silenced THP-1 cells.
authors.affiliation: Beijing Key Laboratory on Drug Resistance in Tuberculosis Research, Beijing 101149, China Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory on Drug Resistance in Tuberculosis Research, Beijing 101149, China Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Weicong
authors.initials: W
authors.lastname: Ren
authors.affiliation: Beijing Key Laboratory on Drug Resistance in Tuberculosis Research, Beijing 101149, China Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, China Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory on Drug Resistance in Tuberculosis Research, Beijing 101149, China Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Chuanyou
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D054908:Extensively Drug-Resistant Tuberculosis / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology* / Q000472:pathogenicity*; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D016207:Cytokines; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Extensively drug-resistant tuberculosis; cytokine; toll-like receptor; virulence