Legionella pneumophila is an intracellular pathogen that causes
Legionnaires' disease in humans. Inbred mouse strains are uniformly resistant to L. pneumophila
infection with the notable exception of A/J, where the chromosome 13 locus Lgn1 renders A/J macrophages permissive to L. pneumophila replication. The mouse Lgn1 region is syntenic with the
spinal muscular atrophy (SMA) locus on human chromosome 5 and includes several copies of the
neuronal apoptosis inhibitory protein (Naip) gene. We have analyzed a possible link among Lgn1, Naip, and macrophage function.
RNA expression studies show that Naip (mostly copy 2)
mRNA transcripts are expressed in macrophage-rich tissues, such as spleen, lung, and liver and are abundant in primary macrophages. 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 significantly less
Naip protein than their nonpermissive C57BL/6J counterpart.
Naip protein expression is increased after phagocytic events.
Naip protein levels during
infection with either virulent or avirulent strains of L. pneumophila 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
Latex beads. The cosegregation of Lgn1 and Naip together with the detected
Naip 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.