Related Experiment Videos
Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila
Edward K Wright1, Sheryl A Goodart, Joseph D Growney
1Howard Hughes Medical Institute, Harvard Medical School, 02115, Boston, MA, USA.
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.
Insights
The gene Naip5 influences susceptibility to Legionella bacteria, the cause of Legionnaires
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Legionella pneumophila causes Legionnaires' Disease by replicating within host macrophages.
- Mouse macrophage permissiveness to Legionella varies significantly between inbred strains.
- A previously mapped locus, Lgn1, on chromosome 13 is associated with this resistance phenotype.
Purpose of the Study:
- To identify the gene responsible for differential host resistance to Legionella intracellular replication.
- To investigate the role of Naip5 (Birc1e) in modulating macrophage permissiveness to Legionella.
Main Methods:
- Detailed recombination mapping to pinpoint the gene's location.
- Analysis of gene expression patterns in different mouse strains.
- Generation of a bacterial artificial chromosome (BAC) transgenic mouse line expressing a specific Naip5 allele.
- Utilizing morpholino-based antisense inhibition to study Naip5 function.
Main Results:
- Naip5 (Birc1e) was identified as a key factor influencing susceptibility to Legionella.
- A BAC transgenic line expressing a nonpermissive Naip5 allele showed reduced Legionella permissiveness in macrophages.
- Inhibition of Naip5 function led to increased macrophage permissiveness for Legionella replication.
Conclusions:
- Polymorphisms in the Naip5 gene are responsible for variations in mouse macrophage permissiveness to Legionella.
- Naip5 is proposed to be a mammalian homolog of plant "resistance" proteins involved in innate immunity.
- Naip5 likely detects bacterial virulence proteins and initiates host defense responses.