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Listeria monocytogenes Desensitizes Immune Cells to Subsequent Ca²⁺ Signaling via Listeriolysin O-Induced Depletion of Intracellular Ca²⁺ Stores

Gekara, Nelson O., Groebe, Lothar, Viegas, Nuno, Weiss, Siegfried
Infection and immunity 2008 v.76 no.2 pp. 857-862
Gram-positive bacteria, Listeria monocytogenes, bacterial toxins, calcium, calcium signaling, cytosol, cytotoxins, host-pathogen relationships, immune evasion, immune system, mutants, pathogens
Listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, is a prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions during L. monocytogenes infection. LLO triggers the influx of Ca²⁺ into host cells as well as the release of Ca²⁺ from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signaling. Interestingly, in this study, we report that prolonged exposure to LLO desensitizes cells to Ca²⁺ mobilization upon subsequent stimulations with LLO. Cells preexposed to LLO-positive L. monocytogenes but not to the LLO-deficient Δhly mutant were found to be highly refractory to Ca²⁺ induction in response to receptor-mediated stimulation. Such cells also exhibited diminished Ca²⁺ signals in response to stimulation with LLO and thapsigargin. The presented results suggest that this phenomenon is due to the depletion of intracellular Ca²⁺ stores. The ability of LLO to desensitize immune cells provides a significant hint about the possible role played by CDCs in the evasion of the immune system by bacterial pathogens.