CD54 EXPRESSION IN CALU-6 IS DIFFERENTIALLY MODULATED BY HUMAN MACROPHAGES STIMULATED WITH OUTBREAK MDR STRAINS OF MYCOBACTERIUM TUBERCULOSIS.

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

Los Cocos

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología (SAI)

Mycobacterium tuberculosis (Mtb) which causes human and animal tuberculosis (TB) mainly infects the lung by interacting with airway epithelium and resident macrophages (Mac). The bronchial epithelium secretes cytokines and chemokines upon interaction with Mtb or after interaction with infected resident Mac. As we have previously demonstrated that the outbreak multidrug-resistant strains of Mtb, M and Ra modulate in vitro innate and adaptative immune response in humans. The aim of the present work was to evaluate the effect of Mtb strains on Calu-6 death and the expression of different PRR, adhesion and APC molecules in this bronchial cell line. To do this, Calu-6 was treated with a) M, Ra and H37Rv strains (Mtb:Calu-6 ratio 10:1), b) Mac stimulated with Mtb from healthy donors (24 h, Mtb: Mac ratio 2 to 5:1; upon informed consent) or c) Mtb-Mac supernatants. Calu-6 death was evaluated by LDH release (ratio 50:1, 24-48 h); CD11b, TLR2, Dectin-1, HLA-DR and CD54 expression by FACS (at 6 h). Results: Even at high ratio, Mtb did not cause Calu-6 death. CD11b, TLR2, Dectin-1 or CD54 were not modulated by direct bacteria recognition independent of the strain (n=8); this fact could be due to low Mtb adhesion/invasion to Calu-6 (2%). H37Rv- and Ra-stimulated Mac enhanced CD54 MFI (p 0.05, n=5) that were further increased by their own supernatants, while M did not. No differences were observed in HLA-DR, Dectin-1 or TLR2 MFI above basal levels. Conclusions: CD54 up-regulation in Calu-6 could be mediated by soluble mediators secreted by Mtb-stimulated Mac and not by direct Mtb recognition. Lack of CD54 upregulation by M strain could be due to differential activation of Mac, being likely a new evasion mechanism employed by M strain to avoid adhesion/infiltration of immune-competent cells to pulmonary epithelium and their further activation, a necessary fact to control Mtb infection.