Production of type I IFN sensitizes macrophages to cell death induced by Listeria monocytogenes.
Type I IFNs (IFN-alpha/beta) modulate innate immune responses. Here we show activation of transcription factor IFN regulatory factor 3, the synthesis of large amounts of IFN-beta mRNA, and type I IFN signal transduction in macrophages infected with Listeria monocytogenes. Expression of the bacterial virulence protein listeriolysin O was necessary, but not sufficient, for efficient IFN-beta production. Signaling through a pathway involving the type I IFN receptor and Stat1 sensitized macrophages to L. monocytogenes-induced cell death in a manner not requiring inducible NO synthase (nitric oxide synthase 2) or protein kinase R, potential effectors of type I IFN action during microbial infections. The data stress the importance of type I IFN for the course of infections with intracellular bacteria and suggest that factors other than listeriolysin O contribute to macrophage death during Listeria infection.
Stockinger
Silvia
S
Vienna Biocenter and University of Vienna, Institute of Microbiology and Genetics, Austria.
Materna
Tilo
T
Stoiber
Dagmar
D
Bayr
Lourdes
L
Steinborn
Ralf
R
Kolbe
Thomas
T
Unger
Hermann
H
Chakraborty
Trinad
T
Levy
David E
DE
Müller
Mathias
M
Decker
Thomas
T
D000818:Animals; D001427:Bacterial Toxins; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000633:toxicity; D006460:Hemolysin Proteins; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014774:Virulence
D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D014157:Transcription Factors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; C038705:hlyA protein, Listeria monocytogenes