Comparative study of interruption of signaling pathways in lung epithelial cell by two different Mycobacterium tuberculosis lineages

Abstract

Alveolar epithelial cell (AEC) provides a replication niche for Mycobacterium tuberculosis. Based on the role of AEC in M. tuberculosis pathogenesis and existence of genetic diversity within this bacterium, we investigated interactions between AEC II and two different M. tuberculosis lineages. We have compared the transcriptome and cytokines/chemokines levels of A549 infected by M. tuberculosis lineage three and four using qRT-PCR and ELISA arrays, respectively. We showed different M. tuberculosis strains induced changes in different effectors that involved in TLRs and NF-κB signaling pathways. We observed different reaction of the studied lineages specifically in pathogenesis, immune evasion mechanism, IL-12/IFN-γ axis, and autophagy. Similar behavior 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 tuberculosis infection. Also, different M. tuberculosis lineages-dependent host-pathogen interactions suggested using only one strain for this kind of research will be controversial.

Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation

“…However, after infection, Calu-3 cells secreted IL-12 and IFN-γ to the same extent whether they were infected in AIC or LCC. IFN-γ and IL-12 are known to be associated with macrophage and dendritic cell responses, although there is evidence that epithelial cells produce these cytokines after infection with microbes (46, 47). IFN-γ has pleiotropic effects on the epithelial cells of the respiratory tract.…”

Air-interfaced colonization model suggests a commensal-like interaction ofNeisseria meningitidiswith the epithelium, which benefit from colonization byStreptococcus mitis

“…However, after infection, Calu-3 cells secreted IL-12 and IFNγ to the same extend whether infection was in AIC or LCC. IFNγ and IL-12 are known to be associated with macrophage and dendritic cells response, although there are evidences that epithelial cells produce these cytokines after infection with microbes 46,47 IFNγ has pleiotropic effects on the epithelial cells of the respiratory tract. This cytokine has been shown to reduce MUC5AC expression, which may lead to a decrease in the barrier property of the respiratory mucus 48 .…”

Autophagy, anoikis, ferroptosis, necroptosis, and endoplasmic reticulum stress: Potential applications in melanoma therapy

“…Necroptosis is a caspase‐independent mechanism involving in the activation of death receptors (Galluzzi, Kepp, Chan, & Kroemer, ). During necroptosis, receptor interacting serine/threonine kinase 3 (PIRK3) and substrate mixed lineage kinase domain‐like (MLKL) play significant roles in activation and execution of cell death, respectively (Hadifar et al, ). Following the phosphorylation of MLKL by PIRK3, MLKL is oligomerized and translocated to the plasma membrane, where it enhances the permeability of membrane through the interaction with a variety of phospholipids.…”