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

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. Access through your institution Buy or

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REFERENCES * Teranishi T, Hirano T, Arima N, Onoue K . Human helper T cell factor(s) (ThF). II. Induction of IgG production in B lymphoblastoid cell lines and identification of T

cell-replacing factor- (TRF) like factor(s) _J Immunol_ 1982 128: 1903–1908 CAS  PubMed  Google Scholar  * Hirano T, Yasukawa K, Harada H _et al_. Complementary DNA for a novel human

interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin _Nature_ 1986 324: 73–76 Article  CAS  Google Scholar  * Hirano T . Interleukin 6 and its receptor: ten years later

_Int Rev Immunol_ 1998 16: 249–284 Article  CAS  Google Scholar  * Hirano T, Nakajima K, Hibi M . Signaling mechanisms through gp130: a model of the cytokine system _Cytokine Growth Factor

Rev_ 1997 8: 241–252 Article  CAS  Google Scholar  * Tanner JW, Chen W, Young RL, Longmore GD, Shaw AS . The conserved box 1 motif of cytokine receptors is required for association with JAK

kinases _J Biol Chem_ 1995 270: 6523–6530 Article  CAS  Google Scholar  * Hibi M, Murakami M, Saito M _et al_. Molecular cloning and expression of an IL-6 signal transducer, gp130 _Cell_

1990 63: 1149–1157 Article  CAS  Google Scholar  * Fukada T, Hibi M, Yamanaka Y _et al_. Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of

STAT3 in anti-apoptosis _Immunity_ 1996 5: 449–460 Article  CAS  Google Scholar  * Takahashi-Tezuka M, Yoshida Y, Fukada T _et al_. Gab1 acts as an adapter molecule linking the cytokine

receptor gp130 to ERK mitogen-activated protein kinase _Mol Cell Biol_ 1998 18: 4109–4117 Article  CAS  Google Scholar  * Nishida K, Yoshida Y, Itoh M _et al_. Gab-family adapter proteins

act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors _Blood_ 1999 93: 1809–1816 CAS  Google Scholar  * Itoh M, Yoshida Y, Nishida K _et al_. Role of

Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen- activated protein kinase activation _Mol Cell Biol_ 2000

20: 3695–3704 Article  CAS  Google Scholar  * Nicholson SE, De Souza D, Fabri LJ _et al_. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2- binding site on the shared

cytokine receptor subunit gp130 _Proc Natl Acad Sci USA_ 2000 97: 6493–6498 Article  CAS  Google Scholar  * Schmitz J, Weissenbach M, Haan S, Heinrich PC, Schaper F . SOCS3 exerts its

inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130 _J Biol Chem_ 2000 275: 12848–12856 Article  CAS  Google Scholar  * Yamanaka Y, Nakajima

K, Fukada T, Hibi M, Hirano T . Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation _EMBO J_ 1996 15:

1557–1565 Article  CAS  Google Scholar  * Ohtani T, Ishihara K, Atsumi T _et al_. Dissection of signaling cascades through gp130 _in vivo_: reciprocal roles for STAT3- and SHP2-mediated

signals in immune responses _Immunity_ 2000 12: 95–105 Article  CAS  Google Scholar  * Unanue ER . Inter-relationship among macrophages, natural killer cells and neutrophils in early stages

of _Listeria_ resistance _Curr Opin Immunol_ 1997 9: 35–43 Article  CAS  Google Scholar  * Kopf M, Baumann H, Freer G _et al_. Impaired immune and acute-phase responses in

interleukin-6-deficient mice _Nature_ 1994 368: 339–342 Article  CAS  Google Scholar  * Dalrymple SA, Lucian LA, Slattery R _et al_. Interleukin-6-deficient mice are highly susceptible to

_Listeria monocytogenes_ infection: correlation with inefficient neutrophilia _Infect Immun_ 1995 63: 2262–2268 CAS  PubMed  PubMed Central  Google Scholar  * Dalrymple SA, Slattery R, Aud

DM _et al_. Interleukin-6 is required for a protective immune response to systemic _Escherichia coli_ infection _Infect Immun_ 1996 64: 3231–3235 CAS  PubMed  PubMed Central  Google Scholar

  * Liu Z, Simpson RJ, Cheers C . Role of interleukin-6 in T-cell activation during primary and secondary infection with _Listeria monocytogenes_ _Infect Immun_ 1995 63: 2790–2792 CAS 

PubMed  PubMed Central  Google Scholar  * Betz UAK, Bloch W, van den Broek M _et al_. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic,

immunological, hepatic, and pulmonary defects _J Exp Med_ 1998 188: 1955–1965 Article  CAS  Google Scholar  * Boyartchuk VL, Broman KW, Mosher RE _et al_. Multigenic control of _Listeria

monocytogenes_ susceptibility in mice _Nat Genet_ 2001 27: 259–260 Article  CAS  Google Scholar  * Rodriguez C, Grosgeorge J, Nguyen VC, Gaudray P, Theillet C . Human gp130 transducer chain

gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11 _Cytogenet Cell Genet_ 1995 70: 64–67 Article  CAS  Google Scholar  * Cheers C, McKenzie

IF . Resistance and susceptibility of mice to bacterial infection: genetics of listeriosis _Infect Immun_ 1978 19: 755–762 CAS  PubMed  PubMed Central  Google Scholar  * Harty JT, Bevan MJ

. Specific immunity to Listeria monocytogenes in the absence of IFN gamma _Immunity_ 1995 3: 109–117 Article  CAS  Google Scholar  * Dai WJ, Bartens W, Kohler G _et al_. Impaired macrophage

listericidal and cytokine activities are responsible for the rapid death of _Listeria monocytogenes_-infected IFN- gamma receptor-deficient mice _J Immunol_ 1997 158: 5297–5304 CAS  PubMed 

Google Scholar  * Lu B, Ebensperger C, Dembic Z _et al_. Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice _Proc Natl Acad Sci USA_ 1998

95: 8233–8238 Article  CAS  Google Scholar  * Tanaka T, Akira S, Yoshida K _et al_. Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor

cytotoxicity by macrophages _Cell_ 1995 80: 353–361 Article  CAS  Google Scholar  * Almeida PF, Almeida RCC . A PCR protocol using inl gene as a target for specific detection of _Listeria

monocytogenes_ _Food Control_ 2000 11: 97–101 Article  CAS  Google Scholar  * Nishibori T, Cooray K, Xiong H _et al_. Correlation between the presence of virulence-associated genes as

determined by PCR and actual virulence to mice in various strains of _Listeria_ spp _Microbiol Immunol_ 1995 39: 343–349 Article  CAS  Google Scholar  * Tonouchi N, Oouchi N, Kashima N _et

al_. High-level expression of human BSF-2/IL-6 cDNA in _Escherichia coli_ using a new type of expression-preparation system _J Biochem (Tokyo)_ 1988 104: 30–34 Article  CAS  Google Scholar 

* Matsuda Y, Harada YN, Natsuume-Sakai S _et al_. Location of the mouse complement factor H gene (cfh) by FISH analysis and replication R-banding _Cytogenet Cell Genet_ 1992 61: 282–285

Article  CAS  Google Scholar  * Matsuda Y, Chapman VM . Application of fluorescence in situ hybridization in genome analysis of the mouse _Electrophoresis_ 1995 16: 261–272 Article  CAS 

Google Scholar  Download references ACKNOWLEDGEMENTS We thank Dr Y Dohi (School of Allied Health Sciences, Osaka University, Japan) for providing the _Listeria monocytogenes_ stock. We thank

Ms R Masuda and Ms A Kubota for secretarial assistance. AUTHOR INFORMATION Author notes * T Ohtani Present address: Department of Immunology, Osaka City University Medical School, 1–4-3,

Asahimachi, Abeno-ku, Osaka, 545–8585, Japan AUTHORS AND AFFILIATIONS * Department of Molecular Oncology (C7), Osaka University Graduate School of Medicine, 2–2 Yamada-oka, Suita, Osaka,

565–0871, Japan D Kamimura, D Fu, T Atsumi, T Ohtani, S J Park, K Ishihara & T Hirano * Chromosome Research Unit, Faculty of Science, Hokkaido University, North 10, West 8, Kita-ku,

Sapporo, 060–0810, Japan Y Matsuda * Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

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for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to T Hirano. ADDITIONAL INFORMATION This work was supported in part by grants from the Ministry of Education,

Culture, Sports, Science and Technology in Japan and the Osaka Foundation for Promotion of Clinical Immunology. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Kamimura, D., Fu, D., Matsuda, Y. _et al._ Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility. _Genes Immun_ 3, 136–143 (2002).

https://doi.org/10.1038/sj.gene.6363825 Download citation * Received: 23 August 2001 * Revised: 16 October 2001 * Accepted: 22 October 2001 * Published: 21 May 2002 * Issue Date: 01 May 2002

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not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * cytokine receptor * gp130 * interferon-gamma *

point-mutation * Listeria monocytogenes