Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages

被引:92
作者
Cervantes, Jorge [1 ]
Nagata, Toshi [2 ]
Uchijima, Masato [1 ]
Shibata, Kiyoshi [3 ]
Koide, Yukio [1 ]
机构
[1] Univ Hamamatsu Sch Med, Dept Infect Dis, Higashi Ku, Shizuoka, Japan
[2] Univ Hamamatsu Sch Med, Dept Hlth Sci, Higashi Ku, Shizuoka, Japan
[3] Univ Hamamatsu Sch Med, Res Equipment Ctr, Higashi Ku, Shizuoka, Japan
关键词
D O I
10.1111/j.1462-5822.2007.01012.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 NH4Cl, 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.
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页码:41 / 52
页数:12
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