Mycobacterium lepraemurium, a well-adapted parasite of macrophages: I. Oxygen metabolites

We measured the release of reactive oxygen intermediaries [ROI (hydrogen pe roxide and superoxide anion)] by murine peritoneal macrophages challenged i n vitro with Mycobacterium lepraemurium (MLM), complement- opsonized yeast, M. bovis BCG, M. phlei, or phorbol myristate acetate (PA). We found that e xcept for MLM, all of the other materials provoked the release of significa nt amounts of hydrogen peroxide and superoxide, MLM entered the macrophages without triggering their oxidative metabolism. Pre-infection of macrophage s with MLM did not alter these cells' capacity to release the normal amount s of ROI in response to other microorganisms or PMA, Killing of MLM did not revert the macrophages' failure to release ROI upon ingestion of the micro organism, nor were macrophages able to produce these toxic metabolites when pre-incubated in the presence of murine gamma interferon (IFN-gamma). MLM has several attributes that allow it to survive within macrophages: a) it i s a nontoxigenic microorganism tit does not harm its host), b) it resists t he harsh conditions of the intraphagolysosomal milieu (a property perhaps d ependent on its thick lipidic envelope), and c) it penetrates the macrophag es without triggering their oxidative response (thus avoiding the generatio n of the toxic intermediaries of oxygen). For these attributes land others discussed in this paper), we recognize MLM as a highly evolved, well-adapte d parasite of macrophages. In addition, the results of the present study prompted the analysis of the biochemical pathways used by MLM and M. bovis BCG to penetrate into their c ellular hosts, a subject now under investigation in our laboratory.