The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection.

Abstract

Baculovirus inhibitor of apoptosis repeat-containing 1 (Birc1) proteins have homology to several germline-encoded receptors of the innate immune system. However, their function in immune surveillance is not clear. Here we describe a Birc1e-dependent signaling pathway that restricted replication of the intracellular pathogen Legionella pneumophila in mouse macrophages. Translocation of bacterial products into host-cell cytosol was essential for Birc1e-mediated control of bacterial replication. Caspase-1 was required for Birc1e-dependent antibacterial responses ex vivo in macrophages and in a mouse model of Legionnaires' disease. The interleukin 1beta converting enzyme-protease-activating factor was necessary for L. pneumophila growth restriction, but interleukin 1beta was not required. These results establish Birc1e as a nucleotide-binding oligomerization-leucine-rich repeat protein involved in the detection and control of intracellular L. pneumophila.

• Authors: Dario S Zamboni, Koichi S Kobayashi, Tiana Kohlsdorf, Yasunori Ogura, E Michelle Long, Russell E Vance, Keisuke Kuida, Sanjeev Mariathasan, Vishva M Dixit, Richard A Flavell, William F Dietrich, Craig R Roy
• Journal: Nature immunology (Nat Immunol) Vol. 7 Issue 3 Pg. 318-25 (Mar 2006) ISSN: 1529-2908 [Print] United States
• PMID: 16444259 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Naip5 protein, mouse
• Neuronal Apoptosis-Inhibitory Protein
• Caspase 1

Topics

• Animals
• Bacterial Translocation
• Caspase 1 (immunology, metabolism)
• Cells, Cultured
• Disease Models, Animal
• Humans
• Immunoblotting
• Legionella pneumophila (physiology)
• Legionnaires' Disease (immunology)
• Macrophages (immunology, microbiology)
• Mice
• Neuronal Apoptosis-Inhibitory Protein (immunology, metabolism)
• Signal Transduction (immunology)
• Transfection