title: Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila.
abstract: BACKGROUND
  Legionella pneumophila is a gram-negative bacterial pathogen that is the cause of Legionnaires' Disease. Legionella produces disease because it can replicate inside a specialized compartment of host macrophages. Macrophages isolated from various inbred mice exhibit large differences in permissiveness for intracellular replication of Legionella. A locus affecting this host-resistance phenotype, Lgn1, has been mapped to chromosome 13, but the responsible gene has not been identified.
  
  
  RESULTS
  Here, we report that Naip5 (also known as Birc1e) influences susceptibility to Legionella. Naip5 encodes a protein that is homologous to plant innate immunity (so-called "resistance") proteins and has been implicated in signaling pathways related to apoptosis regulation. Detailed recombination mapping and analysis of expression implicates Naip5 in the Legionella permissiveness differences among mouse strains. A bacterial artificial chromosome (BAC) transgenic line expressing a nonpermissive allele of Naip5 exhibits a reduction in macrophage Legionella permissiveness. In addition, morpholino-based antisense inhibition of Naip5 causes an increase in the Legionella permissiveness of macrophages.
  
  
  CONCLUSIONS
  We conclude that polymorphisms in Naip5 are involved in the permissiveness differences of mouse macrophages for intracellular Legionella replication. We speculate that Naip5 is a functional mammalian homolog of plant "resistance" proteins that monitor for, and initiate host response to, the presence of secreted bacterial virulence proteins.
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, 02115, Boston, MA, USA.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wright
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Goodart
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Growney
authors.forename: Vey
authors.initials: V
authors.lastname: Hadinoto
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Endrizzi
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Long
authors.forename: Keyvan
authors.initials: K
authors.lastname: Sadigh
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Abney
authors.forename: Isaac
authors.initials: I
authors.lastname: Bernstein-Hanley
authors.forename: William F
authors.initials: WF
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D002478:Cells, Cultured; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D016952:Legionella pneumophila / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000235:genetics* / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D051616:Neuronal Apoptosis-Inhibitory Protein; D011110:Polymorphism, Genetic; D019076:Transgenes
chemical_list: D016375:Antisense Elements (Genetics); C496806:Naip5 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein