[Nontuberculous mycobacteriosis; the present status and in the future. Mechanisms of host resistance to Mycobacterium avium complex and Mycobacterium tuberculosis infection].

In order to know profiles of the antimicrobial action of some microbicidal effector molecules against Mycobacterium avium complex (MAC) and M. tuberculosis (MTB), profiles of collaborating effects among reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) were studied, RNI and FFA exerted synergistic effects in killing MAC and MTB, while the combination of ROI (H2O2-mediated halogenation system) with FFA conversely caused antagonism. The combination of RNI with ROI displayed additive effects in killing MTB, whereas the same combination showed antagonistic effects against MAC. Murine peritoneal macrophages (M phi s) produced and/or released these three antimicrobial effectors in the order ROI, FFA, and RNI in response to cellular stimulation induced by their contact with MAC or MTB organisms. These findings indicate that the collaborating effect of RNI with FFA is crucial for M phi-mediated intracellular killing of MAC and MTB. Secondly, we examined the modes of bacterial growth of MAC and MTB in murine peritoneal M phi s and A-549 type II alveolar epithelial cell line. The growth rate of these organisms was much larger in A-549 cells than in M phi s. In addition, the growth rate of high-virulence MAC (N-260 strain) was significantly larger than that of low-virulence MAC (N-444 strain), when they were residing in M phi or A-549 cells. Although a high virulence MTB (strain Kurono) also showed much more rapid growth in M phi s than did low-virulence MTB (strain H37Ra), such a phenomenon was not observed for their intracellular growth in A-549 cells. MTB exhibited strong cytotoxic effects against M phi s but not against A-549 cells when resided in these cells. On the other hand, MAC organisms did not cause cytotoxicity even in M phi s. Although MAC and MTB infections caused significant increase in RNI production by M phi s but not by A-549 cells, there was no significant relationship between the degree of M phi RNI production by a given mycobacterial organism and its virulence. These findings indicate some important roles of type II alveolar epithelial cells as a target cell for primary invasion and transient growth of mycobacterial organisms in the host lungs.