title: 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.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
authors.forename: Tiana
authors.initials: T
authors.lastname: Kohlsdorf
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ogura
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Long
authors.forename: Russell E
authors.initials: RE
authors.lastname: Vance
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuida
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mariathasan
authors.forename: Vishva M
authors.initials: VM
authors.lastname: Dixit
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: William F
authors.initials: WF
authors.lastname: Dietrich
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D015151:Immunoblotting; D016952:Legionella pneumophila / Q000502:physiology; D007877:Legionnaires' Disease / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
chemical_list: C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D020170:Caspase 1