Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility.
Interleukin-6 family cytokines have been implicated in adaptive and innate immunity, hematopoiesis, and inflammation. This cytokine family shares a signal-transducing receptor subunit called gp130. gp130(F759/F759) knockin mice carry a point mutation at the SHP2-binding site of gp130 due to the replacement of tyrosine-759 (Y759 for human gp130) with phenylalanine (F). To explore the effect of this point mutation on the host response to bacterial infection, gp130(F759/F759) knockin mice were infected with Listeria monocytogenes. gp130(F759/F759) knockin mice began to die at 3 to 4 days post infection (p.i.) and showed higher mortality than did controls. Listeria titers at 3 days p.i. in the peritoneal cavity, spleen, and liver were significantly higher in gp130(F759/F759)knockin mice than in controls. Nitric oxide production, upregulation of the mRNA levels of a variety of cytokines, and listericidal activity in gp130(F759/F759) macrophages were unchanged. However, gp130(F759/F759) knockin mice displayed significantly lower levels of interferon (IFN)gamma in serum and in the culture supernatant from peritoneal exudate cells and splenocytes, in response to Listeria infection. These results suggest that the Y759 point mutation in gp130 attenuates the early phase of defense against Listeria infection, possibly owing to insufficient elevation of IFNgamma levels, and thus gp130 is a possible candidate gene for Listeria susceptibility.
Kamimura
D
D
Department of Molecular Oncology (C7), Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Fu
D
D
Matsuda
Y
Y
Atsumi
T
T
Ohtani
T
T
Park
S J
SJ
Ishihara
K
K
Hirano
T
T
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D050822:Cytokine Receptor gp130; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma; D008088:Listeriosis / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D010770:Phosphotransferases; D017354:Point Mutation; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D007371:Interferon-gamma; D010770:Phosphotransferases