Comparative Profiles of Intramacrophage Behavior of Mycobacterium tuberculosis and Mycobacterium avium Complex with Different Levels of Virulence

Abstract

Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) have different characteristics. For instance, MTB is much more virulent to humans than MAC is (7,20). MTB is transmitted from human to human, but this phenomenon is unknown with MAC (7,12,16). Very small numbers of bacilli are sufficient for MTB to cause pulmonary infection in the lungs of humans, causing an incidence of clinical disease at a ratio of about 5% (12,16). In contrast, in the case of MAC, despite evidence of exposure to the organisms as high as 70%, the incidence of clinical disease is remarkably low ( 10 cases per 100,000 population) (7). Moreover, although MTB causes primary pulmonary infection in immunocompetent hosts, MAC usually causes secondary infection in humans with predisposing conditions in the lungs, such as chronic obstructive pulmonary disease, bronchiectasis, and inactive or active tuberculosis, and it causes opportunistic systemic infection in immunocompromised hosts (7).In this context, there is an enigmatic situation concerning profiles of the interaction of MAC with host macrophages (MΦs), as follows. Although MAC is less virulent for humans and mice than MTB is, MAC organisms can survive and/or replicate in host MΦs, as MTB organisms can (14). Therefore it is of interest to study the profiles of the intracellular behavior of MTB and MAC in host MΦs and the mode of interaction between these organisms and MΦs. In the present study, we examined the profiles of intramacrophage growth of virulent and attenuated MTB and moderate-or lowvirulence MAC strains, cytotoxic effects of these organisms against MΦs, and the mode of RNI production by MΦs infected with these organisms. MTB H37Rv (virulent) and MTB H37Ra (attenuated) strains were used. MAC N-260 (moderate virulence in mice) and MAC N-444 (low virulence in mice) (19) were isolated from patients with MAC infections. They were respectively identified as M. intracellulare and M. avium by a DNA probe test.Macrophage monolayer cultures prepared by seeding 1 10 6 of Zymosan A-induced peritoneal exudate cells of 10-week old BALB/c mice on 16-mm culture wells were incubated in 0.5 ml of Ham's F-12K medium containing 5% fetal bovine serum (FBS) in the presence of MTB H37Rv (8 10 4 CFU/well), MTB H37Ra (3 10 5 CFU/well), MAC N-444 (7 10 5 CFU/well),