Outbreak Multi-drug resistant (MDR) Strains of M. tuberculosis (Mtb) Induce Differential IL-8 Secretion From Human Bronchial Epithelial Cells (Calu-6) Altering Therefore Polymorphonuclear Cells

KVIATCOVSKY DENISE; BALBOA LUCIANA; LANDONI VERÓNICA; COUGOULE CELINE; LOPEZ BEATRIZ; MARIDONNEAU-PARINI ISABELLE; SASIAIN MARÍA DEL CARMEN; DE LA BARRERA SILVIA

Buenos Aires

Congreso; I Meeting LASID FAIC SAI; 2015

Sociedad Argentina de Inmunología y Sociedad Latinoamericana de Inmunodeficiencias

Abstract: Mtb infects the lung by interacting with airway epithelium and resident macrophages. The epithelium not only constitutes an anatomical barrier for bacterial invasion but also responds to pathogens by producing anti-microbial molecules, proinflammatory cytokines and chemokines like IL-8 that recruit macrophages and PMN in order to mount an early inflammatory response and control the infection. Besides, metalloproteinases play an important role in Mtb-induced-tissue destruction and enhance the recruitment of macrophages contributing to granuloma formation and control of bacterial expansion. In this work, we evaluate whether Mtb strains induce differential secretion of IL-8 production and metalloproteinases by Calu-6. Calu-6 were stimulated with MDR strain M and the reference H37Rv strain and the supernatants were tested for IL-8 (ELISA), PMN chemoattractant activity and metalloproteinases secretion. Besides, direct PMN adherence to Calu-6 was determined.Results: 1) Lower IL-8 levels were detected in M-stimulated Calu-supernatants than H37Rv-stimulated (n equal to 5, pminor to 0.05); 2) M-stimulated Calu-supernatants induced lesser chemoattraction of PMN than H37Rv (p minor to0.05); 3) PMN adherence to Calu-6 and metalloproteinase-2/-9 production induced by Mtb strains showed no differences.Conclusion: Similar metalloproteinases production induced by Mtb strains suggests that they may have a similar ability to destroy lung tissue. Moreover, despite showing a similar ability to induce PMN adherence to the epithelium, Mtb strains could differentially stimulate Calu-6 which results in a lower PMN chemoattraction associated to lower IL-8 levels triggered by the M strain. This strategy specifically employed by the M strain could represent an evasion mechanism to avoid infiltration of immune-competent cells to pulmonary epithelium.