Interruption of signaling pathways in lung epithelial cell by Mycobacterium tuberculosis

Abstract

Alveolar epithelial cell (AEC) provides a replication niche for Mycobacterium tuberculosis (M.tb). Based on the role of AEC in M.tb pathogenesis and existence of genetic diversity within this bacterium, we investigated interactions between AEC II and two different M.tb lineages. We have compared the transcriptome and cytokines/chemokines levels of A549 infected by M.tb lineage 3 and 4 using qRT-PCR and ELISA arrays, respectively. We showed different M.tb strains induced changes in different effectors that involved in TLRs and NF-{kappa}B signalling pathways. We observed different reaction of the studied lineages specifically in pathogenesis, immune evasion mechanism, IL-12/IFN-{gamma} axis and autophagy. Similar behaviour was detected in regarding to apoptosis, necroptosis, anti-inflammatory responses and canonical inflammasome. Our findings contribute to elucidate more details in pathogenesis, immune evasion strategies, novel target and druggable pathway for therapeutic intervention and host directed therapy in TB infection. Also, different M.tb lineages-dependent host-pathogen interactions suggested using only one standard strain (e.g. H37Rv) for this kind of research will be controversial.