Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila.
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.
Wright
Edward K
EK
Howard Hughes Medical Institute, Harvard Medical School, 02115, Boston, MA, USA.
Goodart
Sheryl A
SA
Growney
Joseph D
JD
Hadinoto
Vey
V
Endrizzi
Matthew G
MG
Long
E Michelle
EM
Sadigh
Keyvan
K
Abney
Andrew L
AL
Bernstein-Hanley
Isaac
I
Dietrich
William F
WF
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
D016375:Antisense Elements (Genetics); C496806:Naip5 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein