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

Abstract

SummaryListeria monocytogenes induces apoptosis in vitro and in vivo in a variety of cell types. However, the mechanism of cell death in L. monocytogenesinfected 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 4Cl, 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-1b 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.

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

“…Several other bacterial triggers of this atypical cell death modality have been identified, including Shigella flexneri, Listeria monocytogenes, Pseudomonas aeruginosa, Francisella tularensis and the Bacillus anthracis toxin. [144][145][146][147] However, it has become clear that pyroptosis neither constitutes a macrophage-specific process nor a cell death subroutine that only results from bacterial infection. 148 Of note, pyroptotic cells can exhibit apoptotic and/or necrotic morphological features.…”

The NLRP3 inflammasome affects DNA damage responses after oxidative and genotoxic stress in dendritic cells

“…The pro-apoptotic caspase-3, -6, -8, or -9 are not involved in pyroptosis, conversely caspase-1 is not implicated in apoptosis [26]. In addition, mitochondrial integrity is maintained during pyroptosis [27]. Pyroptosis is characterized by plasma membrane breakage, a characteristic that renders this process more similar to necrosis rather than to apoptosis.…”

Cell death in the host response to infection

“…During autophagy, pathogens are surrounded by autophagosomes and delivered to the lysosomes through autophagosome-lysosome fusion. Although apoptosis, pyroptosis and autophagy are generally beneficial to the host, oncosis favors pathogen dissemination monocytogenes, 50 Pseudomonas aeruginosa, 51 Francisella tularensis, 52 Legionella pneumophila, 53,54 Yersinia pseudotuberculosis 55 and Berkholderia pseudomallei 56 (Table 1). Caspase-1 (also known as interleukin (IL)-1b converting enzyme, or ICE) was the first mammalian caspase to be described 57 and is the prototypical member of the inflammatory caspase subfamily.…”