LAUSR

Mycobacteium avium is an intracellular proliferating pathogen and causes chronic refractory respiratory infection. Although apoptosis induced by M. avium has been reported in vitro, the study which determines the role of apoptosis against M. avium infection in vivo remains insufficient. In this study, we investigated the role of apoptosis in M. avium infection in mouse models. Clinically isolated strains of M. avium were used. Tumor necrosis factor (TNF) receptor-1 (TNFR-1) deficient mice (TNFR1-/-) and TNFR-2 deficient mice (TNFR2-/-) background C57Bl/6 were used. M. avium (1 x 10 7 cfu/body) was administered intratracheally into mice. Counting the number of colonies, histology, and apoptosis were investigated. Z-VAD FMK, inhibitor of caspase, was inhaled after M. avium inoculation in wild type mice. In addition, the effect of overexpression of Ik-B alpha on M. avium infection was tested. TNFR1-/- mice was susceptible for M. avium infection compared to both TNFR2-/- mice and wild mice based on the bacterial number and lung histology. More apoptotic cells in the lung were detected in both TNFR2-/- mice and wild mice compared to TNFR1-/- mice. Alveolar macrophages were predominant inflammatory cells in BAL fluids after M. avium instillation. Last, inhalation of Z-VAD-FMK deteriorated M. avium infection compared to vehicle-inhaled control. Overexpression of Ik-B alpha by adenovirus vector attenuated M. avium infection. From the data of our study, apoptosis was considered to have an important role against M. avium in mice. Induction of apoptosis for M. avium -infected cells, mainly macrophage, could be a new strategy for controlling M. avium infection.