Genetic resistance of mice to persistent infection with Mycobacterium lepraemurium in vitro: association with macrophage bactericidal responsiveness to lymphokines and dissociation from production of hydrogen peroxide by macrophages.

Peritoneal and splenic adherent macrophages (SAC) from M. lepraemurium susceptible (C3H/HeJ) and resistant (C57B1/6J) mice were studied for their abilities to generate H2O2 in vitro. Unexpectedly, SAC from the susceptible C3H/HeJ strain produced more H2O2 than those of the resistant C57BL/6J. In vivo sensitization with M. bovis (BCG), or C. parvum increased production of H2O2 by SAC from both strains, whereas in vivo sensitization with M. lepraemurium enhanced H2O2 production only in the C3H/HeJ susceptible strains. In vitro addition of a crude lymphokine enhanced H2O2 production by C3H/HeJ SAC more than by C57BL/6J SAC. In vitro addition of M. lepraemurium caused an inhibition of H2O2 production by SAC from both strains but the inhibition was greater for the resistant C57BL/6J strain. M. lepraemurium phagocytosed in vitro by untreated peritoneal macrophages of both mouse strains were morphologically altered to the same extent. However, the addition of lymphokine dramatically increased the degree of bacterial lysis in only the C57BL/6J strain. These results, support the view that H2O2 plays a limited, if any, role in the protection of the host from M. lepraemurium and may even contribute to susceptibility by inhibiting the host's immune response.