MYCOBACTERIA-BRONCHIAL EPITHELIAL CELLSCROSSTALK THROUGH TYPE I INTERFERON SIGNALING

Background and Aim : The first interaction of mycobacteria with the host occurs in bronchialepithelial cells. Although underlying mechanisms remain unclear, the crosstalk betweenmycobacteria and host cell plays a crucial role in the initiation and subsequent direction of adaptiveimmune responses.Methods : We developed ex vivo and in vivo models using microparticles generated fromMycobacterium abscessus (MAB) to study this crosstalk. For ex vivo model, Normal HumanBronchial Epithelial (NHBE) cells were applied to develop a lung on chip technology. For In vivomodel, we used ۶-week-old age C۵۷Bl/۶ male mice. They were challenged intratracheally withMAB microparticles for ۴ doses with ۳-day intervals.Results : RNAseq analysis identified ۱۷۵۹ differentially expressed genes comparing NHBE cellswith and without MAB microparticles challenge. ۴۱۰ genes had a ۲.۵-fold change (FC) or greater.NHBE cells significantly enriched the IFN I signaling pathway after exposure to MABmicroparticles. Protein overexpression of IFN I family (۲′-۵′-Oligoadenylate Synthetase ۱,Interferon-induced GTP-binding protein Mx۱, Interferon-stimulated gene ۱۵) was found inbronchial epithelial cells following exposure to MAB cell wall microparticles. Significantoverexpression of IFN I family proteins and genes were found in mice lung after intratrachealinoculation of microparticles.Conclusion : Type I IFN initiates a significant local immune response after exposure of bronchialepithelial cells to cell wall of mycobacteria. Our study proposes that “limited bronchial infection”is a more appropriate biologic definition instead of “mycobacteria colonization” whenenvironmental mycobacteria are isolated in sputum without the presence of other diagnosticcriteria of mycobacterial disease.

کلیدواژه ها:

Mycobacteria ، Local immune response ، Normal human bronchial epithelial