Caspase activation may be associated with Mycobacterium avium pathogenicity

Background Mycobacterium avium causes disseminated infection in immunocompromised patients and triggers a process resembling Crohnʹs disease in goats. Colony morphotypes predict pathogenicity. Smooth-transparent (SmT) morphotypes are more virulent and induce less interleukin (IL)-1β and IL-18 production than avirulent smooth-domed (SmD) morphotypes. Caspases are essential for IL-1β and IL-18 production. Methods Caspase activation was examined in human monocytes after M. avium infection. Results Fresh monocytes constitutively expressed caspase-1 mRNA and pro-caspase-1. The M. avium infection increased monocyte caspase-1 mRNA expression. Furthermore, SmD-infected monocytes expressed 2.3-fold higher levels (P <0.05, N = 3) of activated caspases than SmT-infected monocytes. Caspase-1 inhibition significantly reduced IL-1β production by SmT- and SmD-infected monocytes (P <0.05, N = 4). Caspase-3 inhibition inhibited IL-1β production 43.5% ± 8.0% (P <0.02, N = 4) by SmD-infected but not SmT-infected monocytes. Conclusions Decreased mature IL-1β release by SmT-infected monocytes may reflect selective induction of caspase-1 activity but not caspase-3. Differential caspase expression in monocytes after infection may contribute to M. avium pathogenicity in humans.