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YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway

Sauvonnet, N. and Lambermont, I. and van der Bruggen, P. and Cornelis, G. R.. (2002) YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway. Molecular microbiology, Vol. 45, H. 3. pp. 805-815.

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Official URL: http://edoc.unibas.ch/dok/A5259166

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Abstract

Phosphatidylinositol 3-kinase (PI 3-kinase) and its target protein kinase B (Akt) are involved in various processes including internalization, chemotaxis and proliferation. We analysed the activation of Akt in J774 macrophages infected with virulent (pYV+) or avirulent (pYV-) Yersinia enterocolitica. During the early stage of infection with pYV+ and pYV- bacteria, Akt and its targets, glycogen synthase kinase 3 (GSK-3) and forkhead transcription factor (FKHRL1), became phosphorylated. This phosphorylation induction was inhibited by wortmannin and thus dependent on PI 3-kinase. When infection was carried out with pYV+ bacteria but not with pYV- bacteria, Akt and its targets became dephosphorylated at later time points. Using single knock-out mutants in bacterial effector genes, we have determined that the tyrosine phosphatase YopH was responsible for the inactivation of the PI 3-kinase cascade. In macrophages, this inactivation correlated with the downregulation of mRNA coding for monocyte chemoattractant protein 1 (MCP-1), suggesting that YopH inhibits recruitment of macrophages to lymph nodes. We also analysed the effects of Y. enterocolitica infection on the proliferation of T lymphocytes. Consistent with the observation that YopH inactivated the Akt pathway, YopH inhibited PI 3-kinase-dependent secretion of interleukin 2 and proliferation. These data reveal a new effect of YopH in Yersinia pathogenesis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Microbiology (Cornelis)
UniBasel Contributors:Cornelis, Guy R.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Blackwell
ISSN:0950-382X
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:22

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