The important role of perforin against Mycobacterium avium infection in mice

<bold>Background:</bold> <italic>Mycobacterium avium</italic> is an intracellular proliferating pathogen that causes refractory respiratory infection. Perforin contributes to host protection against viral infection and tumor immunity by inducing apoptosis. It is also thought to be important in innate immunity against intracellular pathogen infection, although its role remains controversial. <bold>Objective:</bold> This study investigated the role of perforin in <italic>M. avium</italic> infection prevention using perforin-deficient mice. <bold>Methods:</bold> Clinically isolated strains of <italic>M. avium</italic> were used, along with perforin-deficient and wild-type C57Bl/6 mice. M. avium (1 × 10⁷cfu/body) was administered intratracheally to mice, which were then sacrificed 3, 21, and 60 days after infection. Lung homogenates were inoculated on Middlebrook 7H10 agar plates for counting colonies. Apoptosis in the lungs was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling using lung histology, as well as with a cell death detection kit using lavage fluids. <bold>Results:</bold> Perforin-deficient mice demonstrated severe pulmonary involvement after <italic>M. avium</italic> infection when compared to wild-type mice. Colony counts indicated increased <italic>M. avium</italic> in the lungs of perforin-deficient mice. More apoptotic cells in the lung were detected in WT mice compared to perforin-deficient mice. Many histone-complexed DNA fragments, an indicator of apoptosis, were detected in lavage fluids from wild-type mice compared to fewer in perforin-deficient mice. <bold>Conclusion:</bold> The results show that perforin plays an important role against <italic>M. avium</italic> infection in mice through induction of apoptosis in infected cells. Perforin could be a target for new medication of pulmonary <italic>M. avium</italic> infection.