Role of interferons in LPS hypersensitivity.
The innate immune response to Gram-negative bacteria depends mainly on the ability of the host to respond to the LPS component. Consequently, the state of LPS sensitivity at the time of infection and the numbers of invading bacteria (i.e. the amounts of LPS) are primary factors determining the innate responses provoked by Gram-negative pathogens. LPS sensitivity increases following treatment of mice with live or killed micro-organisms. Two types of sensitization have been recognized, strong, IFN-gamma-dependent and moderate IFN-gamma-independent. IL-12 and IL-18 are intimately involved in the induction of IFN-gamma by bacteria. We showed that Gram-negative bacteria induce IFN-gamma in mice also by an IFN-beta-dependent pathway that requires IL-18 and is independent of IL-12 signaling. This pathway is STAT4 dependent, the activation of which is directly linked to IFN-beta. Further, IFN-beta can be replaced by IFN-alpha. While different components of Gram-negative bacteria induce IL-12 and IL-18, LPS seems to be the only component in these bacteria capable of inducing IFN-beta. Therefore, the IFN-beta pathway of IFN-gamma induction, unlike the IL-12 pathway, proceeds only in LPS responder mice. The IFN-alpha/beta-dependent pathway is expected to play a role whenever IFN-alpha or IFN-beta, and IL-18 are produced concomitantly during infection.
Freudenberg
Marina A
MA
Max-Planck-Institut fü r Immunbiologie, Freiburg, Germany. freudenberg@immunbio.mpg.de
Kalis
Christoph
C
Chvatchko
Yolande
Y
Merlin
Thomas
T
Gumenscheimer
Marina
M
Galanos
Chris
C
D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000472:pathogenicity; D006967:Hypersensitivity / Q000276:immunology*; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D007372:Interferons; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein