Outbreak MDR strains of M. tuberculosis induce differential TNF-alfa secretion by macrophages altering CD54 expression on bronchial epithelial cells

D KVIATCVOVSKY ; BALBOA L; SCHIERLOH P; B LOPEZ; SASIAIN MC; DE LA BARRERA S

Medellín

Congreso; ALAI, Inmunocolombia 2015; 2015

Asociación Latinoamericana de Inmunología.

Mycobacterium tuberculosis (Mtb) infects primarily the lung and is recognized for its ability to evade innate and adaptive host responses. The respiratory epithelium not only acts asa mechanical barrier for gaseous exchange, but also as an immune sentinel. Recent evidence demonstrates that Mtb genotypes would modulate the immune response through different evasion mechanisms. We have shown that the outbreak multidrug-resistant strains of Mtb, M and Ra, differentially modulate in vitro innate and adaptive immune response in humans. The question then arises whether M and Ra strains are able to activate differentially the bronchial epithelium. We have previously demonstrated that the direct interaction between different Mtb strains and bronchial epithelial cells (Calu-6) did not result in the modulation of the phenotype (e.g. TLR-2, CD54 and CD11b expression) or the induction of cell death in Calu-6. Moreover, Mtb strains showed a poor ability to invade the epithelium. However, we did observe a bystander effect from Mtb-stimulated macrophages (Mac) on Calu-6. H37Rv- and Ra-stimulated Mac were able to up-regulate CD54 in Calu-6, while M-stimulated Mac did not. Infunction of these results, we propose to identify the mechanism whereby M strain is not efficient enough to trigger the bystander effect on Calu-6. The aim of the present work was to identify certain soluble factors involved in CD54 regulation in bronchial epithelial cell line Calu-6.Results: Interaction of Calu-6 cells with Mac and its supernatants:i).Incubation of Calu-6 with H37Rv- and Ra-stimulated Mac enhanced CD54 expression, while M-stimulated Mac did not; ii). CD54 increase by Mtb-stimulated Mac supernatants, suggest that soluble factors would mediate CD54 upregulation in bronchial epithelium.Effect of TNF-alfa: i). Mtb strains differentially induced an early TNF-alfa production in Mac being M the lowest inducer. ii) TNF-alfa neutralization inhibited CD54 up-regulation in Calu-6.In conclusion: CD54 modulation on bronchial epithelial cells could be mediated by early TNF-alfa release by Mac. Lack of CD54 up-regulation by M strain could be due to a deficient TNF-alfa production by Mac, being probably a new evasion mechanism employed by this strain to avoidadhesion/infiltration of immune-competent cells to pulmonary epithelium and their further activation, a necessary fact to control Mtb infection.