Dysregulation of the host mevalonate pathway during early bacterial infection activates human TCR gamma delta cells

Kistowska, M. and Rossy, E. and Sansano, S. and Gober, H. J. and Landmann, R. and Mori, L. and De Libero, G.. (2008) Dysregulation of the host mevalonate pathway during early bacterial infection activates human TCR gamma delta cells. European Journal of Immunology, Vol. 38. pp. 2200-2209.

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Official URL: http://edoc.unibas.ch/dok/A6006633

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Primates, but not rodents, have T cell receptor Vgamma9-Vdelta2 T cells bridging innate and adaptive antimicrobial immunity. This T cell population is activated by prenyl pyrophosphates isolated from microbial or eukaryotic cells. Although the microbial metabolites are more active than the cellular ones, their involvement in TCR gammadelta activation during infection has not been studied. Here, we show that, during the initial phases of infections with Escherichia coli and Staphylococcus aureus, TCR gammadelta cells are activated by endogenous mevalonate metabolites. Infections with low bacteria inocula up-regulate the production and accumulation of host-derived TCR gammadelta stimulatory antigens within 1 h, which is followed by a peak of TCR gammadelta cell activation at 5 h. Infections induce the accumulation and dephosphorylation of the hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme of the mevalonate pathway, resulting in increased activity of this enzyme and in increased synthesis of intermediate metabolites. Thus, primates have evolved the ability to readily respond to bacterial infection by sensing the dysregulation of the mevalonate pathway within infected cells, as a mechanism of immediate antimicrobial immunity.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Infection Biology (Landmann-Suter)
UniBasel Contributors:Landmann-Suter, Regine and De Libero, Gennaro
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Verl. Chemie
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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