Natural resistance to mycobacteria: antimicrobial activity and reactive oxygen intermediate releasing functions of murine macrophages.

After infection with Mycobacterium lepraemurium or with M. bovis strain BCG (bacillus Calmette-Guérin), splenic macrophages from mice naturally resistant (NR) to these pathogens (C3H and A/J) spontaneously produced H2O2, whereas splenic macrophages from naturally susceptible (NS) mice (C57BL/6 and Swiss) did not. None of them produced superoxide anion O2-. In addition, NR macrophages had higher levels of superoxide dismutase (SOD) than did NS macrophages. In vivo treatments thought to enhance H2O2 metabolism (phorbol myristate acetate, SOD, Zymosan) decreased M. lepraemurium survival, whereas treatment with diethyl-dithiocarbamate, a potent inhibitor of SOD, had the converse effect. These results favour the hypothesis of a link between natural resistance to BCG (and M. lepraemurium) and H2O2 metabolism, with higher producers being naturally resistant.