Divergent changes in antimicrobial activity after immunologic activation of mouse peritoneal macrophages

To find out whether activated macrophages display a nonspecific enhancement of antibacterial activity, we determined the intracellular killing of bacteria by peritoneal macrophages from CBA and C57BL/10 mice infected with BCG and challenged with mycobacterial antigens (purified protein derivative (PPD]. After in vivo phagocytosis, the rate of in vitro intracellular killing of Listeria monocytogenes by bacillus Calmette-Guérin (BCG)-PPD-activated macrophages from CBA mice increased by a factor of 1.7 and that of those from C57BL/10 mice by a factor of 2.0, relative to the rate in normal resident macrophages. The increased listericidal activity of BCG-PPD-activated macrophages could not have been due to an increased number of peroxidase-positive macrophages because exudate macrophages obtained after i.p. injection of proteose peptone into BCG-infected mice or PPD into control mice, killed ingested Listeria about as efficiently as normal resident macrophages did. In contrast, BCG-PPD-activated macrophages from both mouse strains killed Salmonella somewhat less efficiently and Escherichia coli and Staphylococcus aureus with the same efficiency as normal resident macrophages did. These cells, however, inhibited the intracellular replication of Toxoplasma gondii. Activated peritoneal macrophages from listeria-infected mice showed a similar increase of the rate of intracellular killing of Listeria and absence of change in rate of intracellular killing of Salmonella. Consistent with the in vitro findings, the number of viable L. monocytogenes in the spleen and liver of BCG-infected CBA and C57BL/10 mice decreased during the first 2 days after i.v. injection, whereas Salmonella typhimurium proliferated in these organs of both mouse strains. Checking the state of activation of BCG-PPD-activated macrophages showed that these cells displayed enhanced O2-consumption and H2O2 release after stimulation with phorbol myristate acetate compared with resident macrophages. The present findings show that the antimicrobial activity of immunologically activated macrophages is not uniformly increased: for certain microorganisms (L. monocytogenes, T. gondii), this effector function is enhanced, whereas for others (S. typhimurium, S. aureus, E. coli), it is not.