Genetic Resistance of Mice to Persistent Infection with Mycobacterium Lepraemurium in Vitro: Association with Macroprage 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 hose 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. leraemurium 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. leraemurium phagocytosed in vitro by untreated peritoneal macropbages of both mouse strains were morphologically altered to the aame 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.