Experimental Reactivation of Pulmonary <i>Mycobacterium avium</i> Complex Infection in a Modified Cornell-Like Murine Model

<div><p>The latency and reactivation of <i>Mycobacterium tuberculosis</i> infection has been well studied. However, there have been few studies of the latency and reactivation of <i>Mycobacterium avium</i> complex (MAC), the most common etiological non-tuberculous <i>Mycobacterium</i> species next to <i>M</i>. <i>tuberculosis</i> in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of <i>M</i>. <i>avium</i> and <i>M</i>. <i>intracellulare</i>. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in <i>M</i>. <i>avium</i> infection) or sulfasalazine (four out of six mice in both <i>M</i>. <i>avium</i> and <i>M</i>. <i>intracellulare</i> infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection.</p>