Outbreak MDR Strains of M. tuberculosis (Mtb) Induce Differential TNF- Secretion by Macrophages Altering CD54 Expression on Bronchial Epithelial Cells

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

Congreso; Congreso SAI_SAIC; 2014

Mtb infects mainly the lung by interacting with airway epithelium and resident macrophages (Mac). The bronchial epithelium secretes cytokines (CKs) upon interaction with Mtb or infected Mac. We have previously demonstrated that certain soluble factors released by Mac stimulated with MDR strains, M and Ra differentially modulate CD54 expression in the human bronchial epithelial cell line Calu-6. Thus, the aim of this work was to identify those soluble factors involved in CD54 regulation in airway epithelial cells. To do so, monocytes derived Mac from healthy donors were stimulated with M, Ra or H37Rv strains for 6h at Mtb:Mac 1:2 or 1:5 ratios and TNF-alpha levels were determined by FACS and ELISA. In addition, Calu-6 cells were co-cultured with Mac or stimulated Mac-derived supernatants (Mac-SN) and CD54 expression was evaluated. To confirm the role of CKs on CD54 modulation, Calu-6 cells were treated with Mac-SN in the presence of a synthetic soluble TNF-alpha receptor (Etanercept) and/or anti-IL-1beta monoclonal antibody. Results: 1) M-stimulated Mac produced lower levels of released (n=7) or intracellular(n=9) TNF-alpha than H37Rv-stimulated Mac (p