The immunology of other mycobacteria: M. ulcerans, M. leprae

Abstract

Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.

Keywords: Buruli ulcer; Diagnosis; Immune evasion; Immunopathology; Leprosy; Polarization of immune responses; Vaccine design.

Fig. 1

Structure of mycolactone A/B

Fig. 2

Ridley and Jopling classification and unusual forms of leprosy, associated with the degree of the bacillary load and the immune response. PNL pure neural leprosy, DLL diffuse lepromatous leprosy, LL lepromatous leprosy, BL borderline lepromatous leprosy, BB borderline borderline leprosy, BT borderline tuberculoid leprosy, TT tuberculoid leprosy. Adapted from [150]