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Infect. Immun. doi:10.1128/IAI.01779-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cytolysin-dependent phagosomal escape is required but not sufficient for the induction of Th1 immune response against Listeria infection: A distinct role of listeriolysin O as determined by cytolysin gene replacement

Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan

^* To whom correspondence should be addressed. Email: mituyama{at}mb.med.kyoto-u.ac.jp.

	Abstract

Listeria monocytogenes (LM) evades the antimicrobial mechanisms of macrophages by escaping from the phagosome into the cytosolic space via a unique cytolysin that targets the phagosomal membrane, listeriolysin O (LLO) encoded by hly. IFN-, which is known to play a pivotal role in the induction of Th1-dependent protective immunity in mice, appears to be produced, depending on the bacterial virulence factor. To determine whether the LLO molecule (the major virulence factor of LM) is indispensable or the phagosomal escape of bacteria is sufficient to induce IFN- production, we first constructed a hly-deleted mutant of LM and then established isogenic LM mutants expressing LLO or ivanolysin O (ILO) encoded by ilo from L. ivanovii. LLO-expressing LM was highly capable of inducing IFN- production and Listeria-specific protective immunity while the hly-deleted mutant was not. In contrast, the level of IFN- induced by ILO-expressing LM was significantly lower both in vitro and in vivo, despite the ability of this strain for phagosomal escape and intracellular multiplication at a level equivalent to LLO-expressing LM. Only a negligible level of protective immunity was induced in mice against challenge with LLO- and ILO-expressing LM. These results clearly show that phagosomal escape is a prerequisite, but is not sufficient for IFN--dependent Th1 response against LM, and some distinct molecular nature of LLO is indispensable for the final induction of IFN- that is essentially required to generate a Th1-dependent immune response.

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• Hara, H., Tsuchiya, K., Nomura, T., Kawamura, I., Shoma, S., Mitsuyama, M. (2008). Dependency of Caspase-1 Activation Induced in Macrophages by Listeria monocytogenes on Cytolysin, Listeriolysin O, after Evasion from Phagosome into the Cytoplasm. J. Immunol. 180: 7859-7868 [Abstract] [Full Text]