The neuronal apoptosis inhibitory protein (Naip) is expressed in macrophages and is modulated after phagocytosis and during intracellular infection with Legionella pneumophila

Legionella pneumophila is an intracellular pathogen that causes Legionnaire s' disease in humans, Inbred mouse strains are uniformly resistant to L. pn eamophila infection with the notable exception of A/J, where the chromosome 13 locus Lgn1 renders. A/J macrophages permissive to L, pneumophila replic ation. The mouse Lgn1 region is syntenic with the spinal muscular atrophy ( SMA) locus on human chromosome 5 and includes several copies of the neurona l apoptosis inhibitory protein (Naip) gene. We have analyzed a possible lin k among Lgn1, Naip, and macrophage function. RNA expression studies show th at Naip (mostly copy 2) mRNA transcripts are expressed in macrophage-rich t issues such as spleen, lung, and liver and are abundant in primary macropha ges, Immunoblotting and immunoprecipitation analyses identify Naip protein expression in mouse macrophages and in macrophage cell lines RAW 264.7 and J774A, Interestingly, macrophages from permissive A/J mice express signific antly less Naip protein than their nonpermissive C57BL/6J counterpart. Naip protein expression is increased after phagocytic events, Naip protein leve ls during infection with either virulent or avirulent strains of L, pneumop hila increase during the first 6 h postinfection and remain elevated during the 48-h observation period, This enhanced expression is also observed in macrophages infected with Salmonella typhimurium, Likewise, an increase in Naip protein levels in macrophages is observed 24 h after phagocytosis of L ates beads. The cosegregation of Lgn1 and Naip together with the detected N aip protein expression in host macrophages as well as its modulation after phagocytic events and during intracellular infection make it an attractive, candidate for the Lgn1 locus.