Caspase activation may be associated with Mycobacterium avium pathogenicity

Hiroe Shiratsuch1, Marc D Basson

  • 1Department of Surgery, Wayne State University, Research Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI 48201, USA. hiroesh@msn.com

Abstract

Insights

Mycobacterium avium infection impacts caspase activity in human monocytes. Virulent M. avium strains may suppress caspase-3, influencing interleukin-1beta production and disease severity.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Biology

Background:

  • Mycobacterium avium (M. avium) infection causes disseminated disease in immunocompromised individuals.
  • M. avium infection in goats mimics Crohn's disease, with colony morphotypes correlating to pathogenicity.
  • Smooth-transparent (SmT) M. avium morphotypes are more virulent, inducing lower levels of interleukin (IL)-1beta and IL-18 compared to avirulent smooth-domed (SmD) morphotypes.

Purpose of the Study:

  • To investigate caspase activation in human monocytes following M. avium infection.
  • To determine the role of differential caspase activity in M. avium pathogenicity.

Main Methods:

  • Human monocytes were infected with M. avium.
  • Caspase-1 and caspase-3 activation and mRNA expression were analyzed.
  • The impact of caspase inhibition on IL-1beta production was assessed.

Main Results:

  • M. avium infection upregulated caspase-1 mRNA expression in monocytes.
  • Monocytes infected with SmD morphotypes showed significantly higher activated caspase levels than those infected with SmT morphotypes.
  • Caspase-1 inhibition reduced IL-1beta production in both SmT- and SmD-infected monocytes.
  • Caspase-3 inhibition reduced IL-1beta production in SmD-infected monocytes but not in SmT-infected monocytes.

Conclusions:

  • Differential caspase activation, particularly caspase-1, occurs in human monocytes upon M. avium infection.
  • The selective induction of caspase-1 and lack of caspase-3 activation by virulent SmT morphotypes may contribute to M. avium pathogenicity.
  • These findings highlight the role of host caspase responses in M. avium pathogenesis.

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