Contrary to BCG, MLM fails to induce the production of TNFx and NO by macrophages

ABSTRACT

Pathogenic mycobacteria must possess efficient survival mechanisms to resist the harsh conditions of the intraphagosomal milieu. In this sense, Mycobacterium lepraemurium (MLM) is one of the most evolved intracellular parasites of murine macrophages; this microorganism has developed a series of properties that allows it not only to resist, but also to multiply within the inhospitable environment of the phagolysosome. Inside the macrophages, MLM appears surrounded by a thick lipid-envelope that protects the microorganism from the digestive effect of the phagosomal hydrolases and the acid pH. MLM produces a disease in which the loss of specific cell-mediated immunity ensues, thus preventing activation of macrophages. In vitro, and possibly also in vivo, MLM infects macrophages without triggering the oxidative (respiratory burst) response of these cells, thus preventing the production of the toxic reactive oxygen intermediaries (ROI). Supporting the idea that MLM is within the most evolved pathogenic microorganisms, in the present study we found, that contrary to BCG, M. lepraemurium infects macrophages without stimulating these cells to produce meaningful levels of tumor necrosis factor alpha (TNF alpha) or nitric oxide (NO). Thus, the ability of the microorganisms to stimulate in their cellular hosts, the production of ROI and RNI (reactive nitrogen intermediates), seems to be an inverse correlate of their pathogenicity; the lesser their ability, the greater their pathogenicity.