Differential immune cell response to Mycobacterium intracellulare colony morphotypes

Abstract

Abstract Mycobacterium intracellulare is an opportunistic pathogen which causes disease in immunocompromised individuals. Like several other nontuberculous mycobacteria (NTM) species, a single strain of M. intracellulare forms bacterial colonies with varying morphologies; however, the relative virulence and immunogenicity of differing M. intracellulare morphotypes are unknown. We have obtained a strain of M. intracellulare isolated from an infected patient and further subcultured it to distinguish the component colony morphotypes present within the parent isolate. To determine whether these distinct colony morphotypes have the ability to stimulate differential immune responses in an infected host, C57BL/6J mice were aerosol infected with either the parent clinical strain or each of the isolated component colony morphotypes. Differential immune response and virulence characteristics of the morphotypes were evaluated by tracking host bacterial load, cytokine expression profiles, and histology. In addition, bone marrow-derived macrophages were isolated and infected in vitro with the different morphotypes and parent isolate. From this study, we have found that the component colony morphotypes are able to differentially activate macrophages and affect the host immune response to infection. These results may establish an important immunological basis for patient clinical outcomes.