Differential requirement for interferon-γto restrict the growth of or eliminate some recently identified species of nontuberculous mycobacteriain vivo

Abstract

SUMMARYIn recent years, a number of newly identified species of the genus Mycobacterium (M.) have been isolated from tissues of both immunocompetent and immunocompromised patients, e.g. M. celatum, M. intermedium, M. interjectum, M. bohemicum, M. conspicuum, M. confluentis, M. heidelbergense, M. lentiflavum, and M. branderi. Little is known about their in vivo virulence characteristics and the host factors predisposing to infection with these strains. In an effort to elucidate the pathogenesis of these nontuberculous mycobacterial species, BALB/c and syngeneic IFNg-deficient (GKO) mice were intravenously infected with 10 6 colony forming units of each of these species, and bacterial growth in infected organs and the development of splenomegaly and granulomatous liver lesions were examined for a period of 3 months. Based on their in vivo virulence, mycobacterial strains could be divided into three major groups: (i) Most species examined either grew progressively or persisted at plateau levels in the livers and spleens of immunocompetent mice, and their growth was increased in GKO mice. (ii) M. heidelbergense, M. intermedium and another species not officially accorded separate taxonomical status were eliminated in BALB/c mice, but persisted in GKO mice. (iii) M. confluentis, M. lentiflavum and another novel species were eradicated even in the absence of IFNg. Nontuberculous mycobacterial species differed widely in their capacity to induce splenomegaly and lymphadenopathy in GKO mice. In conclusion, IFNg is a crucial determinant of infection outcome with most, but not all opportunistic mycobacterial species.

Impact of Genotypic Studies on Mycobacterial Taxonomy: the New Mycobacteria of the 1990s

“…From such a survey, unusually rich for a species recognized less than 4 years ago, two major observations emerge: M. bohemicum should be regarded as a potential pathogen, and natural water is one of its reservoirs. The virulence of the species also seems confirmed: following intravenous infection of syngeneic gamma interferon-deficient and BALB/c mice with M. bohemicum, also the latter, nonimmunocompromised animals developed splenomegaly and granulomatous liver lesions (36).…”

“…Nevertheless, the virulence of the species does not seem lower than that of other opportunistic agents like MAC and M. genavense, especially since the disseminated mycobacterial infection was probably a major cause of death in both subjects. The virulence in vivo of M. conspicuum seems to be confirmed by the development of splenomegaly and granulomatous liver lesions not only in syngeneic gamma interferon-deficient mice but also in BALB/c mice following intravenous infection (36).…”

“…Such a hypothesis also seems confirmed by the experimental inoculation of M. celatum into BALB/c and syngeneic gamma interferon-deficient mice. It gave rise to splenomegaly and granulomatous liver lesions in both immunocompetent and immunodeficient animals, demonstrating the high virulence of the strain (36).…”

“…No doubt exists about the potential pathogenicity of the species, as confirmed also by the investigation of virulence in vivo, carried out by experimental infection of BALB/c and syngeneic gamma interferon-deficient mice, which gave rise to splenomegaly and granulomatous liver lesions in both animals (36).…”

Pulmonary Mycobacterium intermedium Disease in an Elderly Man with Healed Pulmonary Tuberculosis

“…One might still argue that the present case does not have the symptoms compatible with NTM disease (1). It should be noted, however, that the clinical criteria set by the American Thoracic Society are based on the lung disease caused by M. avium, which is more virulent than M. intermedium, at least in mice, and hence the latter might cause much more subtle disease (2,6).…”