Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility

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Abstract
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. gp130F759/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, gp130F759/F759 knockin mice were infected with Listeria monocytogenes. gp130F759/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 gp130F759/F759knockin mice than in controls. Nitric oxide production, upregulation of the mRNA levels of a variety of cytokines, and listericidal activity in gp130F759/F759 macrophages were unchanged. However, gp130F759/F759 knockin mice displayed significantly lower levels of interferon (IFN)γ 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 IFNγ levels, and thus gp130 is a possible candidate gene for Listeria susceptibility.