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

• Published in: Nature Immunology Vol. 7; no. 3; pp. 318 - 325
• Main Authors: Roy, Craig R, Zamboni, Dario S, Kobayashi, Koichi S, Kohlsdorf, Tiana, Ogura, Yasunori, Long, E Michelle, Vance, Russell E, Kuida, Keisuke, Mariathasan, Sanjeev, Dixit, Vishva M, Flavell, Richard A, Dietrich, William F
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2006; Nature Publishing Group
• Subjects: Animals; Bacterial Translocation; Baculovirus; Biomedical and Life Sciences; Biomedicine; Caspase 1 - immunology; Caspase 1 - metabolism; Cells, Cultured; Disease Models, Animal; Humans; Immune system; Immunoblotting; Immunology; Infectious Diseases; Legionella pneumophila; Legionella pneumophila - physiology; Legionnaire's disease; Legionnaires' Disease - immunology; Macrophages - immunology; Macrophages - microbiology; Mice; Neuronal Apoptosis-Inhibitory Protein - immunology; Neuronal Apoptosis-Inhibitory Protein - metabolism; Pathogens; Signal Transduction - immunology; Transfection; Translocation
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1305

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 1β converting enzyme–protease-activating factor was necessary for L. pneumophila growth restriction, but interleukin 1β 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 .