Membrane damage and interleukin-1 production in murine macrophages exposed to listeriolysin O

Abstract

To obtain some insight into the interaction between listeriolysin 0 (LLO) and the macrophage membrane, we examined the effect of purified Listeria monocytogenes hemolysin on the viability and functions of mouse peritoneal exudate macrophages. The study showed that purified LLO impaired a variety of functions of the * Corresponding author.

Listeriolysin O: cholesterol inhibits cytolysis but not binding to cellular membranes

“…It was tempting to speculate that preincubation with cholesterol would saturate cholesterol-binding sites, thus preventing binding to cholesterol present in the membranes of target cells. However, despite being pretreated with cholesterol, such LLO-cholesterol complexes were capable of triggering cytokine expression (Nishibori et al, 1996), release of IL-1 (Yoshikawa et al, 1993) and stimulation of the phosphatidylinositol cascade (Sibelius et al, 1996). These observations suggested that an interaction with the cellular membrane had taken place even although cytolysis by LLO was abolished by cholesterol treatment.…”

Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis.

“…Listeriolysin O, a 58-kDa thiol-activated hemolysin, is the best-characterized virulence factor of Listeria monocytogenes and is necessary for the intracellular survival of the organism. Two recent reports have established that this toxin can potently induce murine macrophages to synthesize both IL-1 mRNA transcripts and protein (231,256). A toxin from Bordetella pertussis, termed pertussis toxin, which is a protein, has also been shown to enhance IL-4 production, which may explain the ability of this toxin to upregulate immunoglobulin E responses (156).…”

An Arcanobacterium(Actinomyces) pyogenes Mutant Deficient in Production of the Pore-Forming Cytolysin Pyolysin Has Reduced Virulence

“…Listeriolysin O (LLO) contributes significantly to the pathogenicity of L. monocytogenes, as the toxin is essential for bacterial escape from the phagolysosome, and mutants in LLO production are avirulent (12). LLO is also cytotoxic for murine macrophages (48) and induces the expression of a variety of host cytokines (26,36).…”

“…One possible role of PLO in pathogenesis may be to deplete host macrophages (and neutrophils), protecting bacteria from phagocytosis. LLO can directly inhibit macrophage phagocytosis of opsonized erythrocytes (48), and PLY inhibits the bacteriocidal activity of neutrophils (37) and monocytes (34). Although TACYs such as LLO and PLY upregulate expression of various cytokines such as interleukin-1␤ (IL-1␤), IL-6, IL-12, and tumor necrosis factor alpha by macrophages and monocytes (19,26,36), depletion of phagocytic cells may lead to decreased cytokine signaling, further impairing host responses against infection.…”