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.

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.