Caspase activation may be associated with Mycobacterium avium pathogenicity.
BACKGROUND
Mycobacterium avium causes disseminated infection in immunocompromised patients and triggers a process resembling Crohn's disease in goats. Colony morphotypes predict pathogenicity. Smooth-transparent (SmT) morphotypes are more virulent and induce less interleukin (IL)-1beta and IL-18 production than avirulent smooth-domed (SmD) morphotypes. Caspases are essential for IL-1beta 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-1beta production by SmT- and SmD-infected monocytes (P <0.05, n = 4). Caspase-3 inhibition inhibited IL-1beta production 43.5% +/- 8.0% (P <0.02, n = 4) by SmD-infected but not SmT-infected monocytes.


CONCLUSIONS
Decreased mature IL-1beta 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.
Shiratsuch
Hiroe
H
Department of Surgery, Wayne State University, Research Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI 48201, USA. hiroesh@msn.com
Basson
Marc D
MD
D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D009162:Mycobacterium avium / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics; D014774:Virulence
D007375:Interleukin-1; D012333:RNA, Messenger; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1