The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of

Legionella pneumophila infection

Nature Immunology 7, 318-325 (2006)

Speaker：陳家如                         Time：15:10~16:00, Mar 29, 2006

Commentator：徐麗君 老師                Place：Room 601

Abstract:

Legionella pneumophila is an intracellular pathogen that causes an acute form of pneumonia called Legionnaires disease. Essential for pathogenesis is the ability of L. pneumophila to replicate in macrophages. The intracellular survival strategy of L. pneumophila involves segregation in a replication vacuole derived from the endoplasmic reticulum. In contrast with human cells, macrophages from most inbred strains of mice are non-permissive for L. pneumophila replication, with the exception of the A/J strain. This phenomenon is likely genetically controlled by the mouse birc1e(naip5) gene located within the Lgn1 locus on chromosome 13¹. The Birc1e protein contain three adjacent N-terminal BIR domains, a centrally located nucleotide-binding oligomerization domain (Nod) and a C-terminal leucine-rich repeat (LRR) domain. However, the Birc1e protein shows sequence similarity to the Nod-LRR protein family, its function is not clear. Therefore, the authors wanted to know the functional differences between the A/J and the non-permissive strain, C57BL/6 Birc1e proteins and their roles in control of L. pneumophila infection. In previous study, isolated BIR domains from human Birc1 inhibit cell death caused by ectopic production of caspase-1 in HEK293 cells. The authors suggested that caspase-1-dependent activities can provide ‘readouts’ for Birc1-mediated responses. So, they have adapted this HEK293 cell assay and found that Birc1e-mediated caspase-1-dependent cell death of HEK293 cells by L. pneumophila infection. The Birc1e activation required the delivery of bacterial molecules into host cytosol. They also found that caspase-1 was required for Birc1e-dependent antibacterial responses ex vivo in macrophages and in a mouse model of Legionnaires’ disease. The interleukin 1b converting enzyme–protease-activating factor was necessary for L. pneumophila growth restriction, but interleukin 1b was not required. These results establish Birc1e as a Nod-LRR protein involved in the detection and control of intracellular L. pneumophila².

References:

1. Diez, E. et al. Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila. Nature Genetic 33, 55–60 (2003).

2. Dario S Zamboni and Craig R Roy et al. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nature Immunology 7, 318-325 (2006)