Type I IFN are host modulators of strain-specific Listeria monocytogenes virulence.
Type I IFN (IFN-I) increase the sensitivity of cells and mice to lethal infection with Listeria monocytogenes. Therefore the amount of IFN-I produced during infection might be an important factor determining Listeria virulence. Two commonly used strains of L. monocytogenes, EGD and LO28, were identified as, respectively, low and high inducers of IFN-I synthesis in infected macrophages. Increased IFN-I production resulted from the stronger ability of the LO28 strain to trigger the IRF3 signalling pathway and correlated with an increased sensitization of macrophages to lethal infection. In contrast, stimulation of NFkappaB, MAPK, or inflammasome signalling by the LO28 and EGD strains did not differ significantly. The LO28 strain was more virulent in wild-type (wt) C57/BL6 mice than the EGD strain whereas both strains were similarly virulent in IFN-I receptor-deficient C57/BL6 mice. Together our data suggest that isolates of wt L. monocytogenes differ in their ability to trigger the IRF3 signalling pathway and IFN-I production, and that the amount of IFN-I produced during infection is an important determinant of Listeria virulence.
Reutterer
Benjamin
B
Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Dr Bohr-Gasse 9/4, A-1030 Vienna, Austria.
Stockinger
Silvia
S
Pilz
Andreas
A
Soulat
Didier
D
Kastner
Renate
R
Westermayer
Sandra
S
Rülicke
Thomas
T
Müller
Mathias
M
Decker
Thomas
T
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D015398:Signal Transduction; D013045:Species Specificity; D014774:Virulence
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C508032:Ifnar1 protein, mouse; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; C038705:hlyA protein, Listeria monocytogenes