Relationship of human apoptosis inhibitor NAIP1 between natural resistance against Legionellainfection

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Macrophages from C57BL/6 mice restrict growth of Legionella pneumophila. Restriction of bacterial growth is dependent on cell death which requires caspase-1 and Naip5. On the other hand, A/J mouse strain carries a defective Naip5allele, whose macrophages resultin permissiveness to L. pneumophilareplication. We found murine RAW264 macrophage cells exceptionally supported bacterial growth and failed to induce caspase-1-mediated cell death. C57BL/6 Naip5 restored susceptibility to L. pneumophilaand impaired induction of cell death,indicating RAW264 harbors a defect in endogenous Naip5 function. Human NAIP, structural homolog of Naip5, also restored Naip5-deficiency in RAW264 cells. A/J mice expressing human NAIP in macrophages exhibited improved bacterial clearance and decreased mortality when challenged with L. pneumophilaat lung. These results suggest that human NAIP is a functional homolog of murine Naip5 and contributes host's defense against L. pneumophilaby inducing caspase-1-dependent cell death.