The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection.
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.
Zamboni
Dario S
DS
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Kobayashi
Koichi S
KS
Kohlsdorf
Tiana
T
Ogura
Yasunori
Y
Long
E Michelle
EM
Vance
Russell E
RE
Kuida
Keisuke
K
Mariathasan
Sanjeev
S
Dixit
Vishva M
VM
Flavell
Richard A
RA
Dietrich
William F
WF
Roy
Craig R
CR
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
C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D020170:Caspase 1