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.
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
Hiroe
H
Shiratsuch
Marc D
MD
Basson
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