Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages.
Listeria monocytogenes induces apoptosis in vitro and in vivo in a variety of cell types. However, the mechanism of cell death in L. monocytogenes-infected macrophages was initially reported to be distinct from apoptosis. Here, we studied the mechanism of L. monocytogenes-induced cell death using sensitive fluorescent techniques. We found that caspase-1 activation preceded cell death of macrophages infected with L. monocytogenes, using fluorogenic substrates. Caspase-1 activation was diminished after infection with wild-type L. monocytogenes when cells were treated with NH(4)Cl, or if they were infected with a listeriolysin mutant that cannot escape from the phagolysosome. Mitochondrial membrane integrity was preserved during the infection. A particular mechanism of cell death, recently termed 'pyroptosis', is associated with infection by intracellular microorganisms, and has an inherent pro-inflammatory character, due to involvement of caspase-1 activation with consequent IL-1 beta and IL-18 production. Cell death through caspase-1 activation would constitute a defence mechanism of macrophages which induces cell death to eliminate the bacteria's intracytosolic niche and recruits early host's defences through the secretion of inflammatory cytokines.
Cervantes
Jorge
J
Department of Infectious Diseases, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Nagata
Toshi
T
Uchijima
Masato
M
Shibata
Kiyoshi
K
Koide
Yukio
Y
D000818:Animals; D020170:Caspase 1 / Q000096:biosynthesis*; D016923:Cell Death; D002460:Cell Line; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D051336:Mitochondrial Membranes / Q000502:physiology
D020170:Caspase 1