Evaluation of the immune response induced by drug resistant Mycobacterium tuberculosis strains

YOKOBORI NOEMÍ; GEFFNER LAURA,; SCHIERLOH PABLO; ALEMÁN MERCEDES; RITACCO VIVIANA; VESCOVO MARISA; GARCÍA ANA; LÓPEZ BEATRIZ; BARRERA LUCIA; DE LA BARRERA SILVIA; SASIAIN MC

Río de Janeiro

Congreso; Congreso Internacional de Inmunología; 2007

Multi-drug resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (Mtb)strains resistant to, at least, isoniazid and rifampicin. In Argentina MDR-TB outbreaks emerged in the early 90’s. Epidemiological, bacteriological and RFLP genotyping data allowed theidentification of the Muñiz strain (M) belonging to the Haarlem lineage and responsible for clustered MDR-TB cases. Besides, the 410 strain which is genetically linked to M and had caused a single MDR-TB was also identified. Inhibition of macrophage apoptosis was proposed as a strategy of Mtb to subvert host immunity by reducing their microbicidal capacity and the cross-presentation of Mtb antigens. The aim of our study was to characterize in vitro the immune response induced by M strain in healthy donors. We evaluated lymphocyte proliferation (Thymidine incorporation), cell surface markers, cytokine production and apoptosis (AnnexinV/PI) by flow cytometry in peripheral blood monocyte derived macrophages (MDM) pulsed with heated M and the standard H37Rv strains. In PPD+ donors lower lymphocyte proliferation was observed with M (n=7; p<0.05). Although no differences were found in IL-12 production, M produced lower percentages of MDM-TNF + cells than H37Rv (n=6; p<0.05). MDM-induced apoptosis was lower with M than H37Rv (% H37Rv:41.8±6.9; M:26.2±7.5, n=6; p<0.01). This fact would be mediated by an inhibitory mechanism triggered by M strain (MDMH37Rv- induced apoptosis: 49.5± 7.3 %; MDM pretreated with M: 31.8± 6.1%; p<0.05) because the inhibition was not observed in MDM pretreated with 410 strain. These data suggest that M strain would be less antigenic and more virulent than H37Rv and 410 strains.