Cell invasion and strain dependent induction of suppressor of cytokine signaling-1 by Toxoplasma gondii

Stutz, A., Kessler, H., Kaschel, M., Meissner, M. and Dalpke, A.H. (2012) Cell invasion and strain dependent induction of suppressor of cytokine signaling-1 by Toxoplasma gondii. Immunobiology, 217(1), pp. 28-36. (doi:10.1016/j.imbio.2011.08.008)

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Publisher's URL: http://dx.doi.org/10.1016/j.imbio.2011.08.008

Abstract

Toxoplasmagondii is an intracellular parasite that has to cope with the microbicidal actions of IFNγ. Previously we reported that parasite-mediated induction of suppressor of cytokinesignaling protein 1 (SOCS1) contributes to inhibition of IFNγ signaling. However, the signaling requirements remained elusive. We now show that induction of SOCS1 and inhibition of nitric oxide production by IFNγ was independent of stimulation of Toll-like receptors. Instead, infection by T. gondii resulted in induction of egr transcription factors which have been reported to regulate SOCS expression. Indeed, induction of egr2 as well as SOCS1 was dependent on p38 MAP kinase and blockade of egr inhibited SOCS1 expression. Moreover, we found that Mic8, a previously identified invasion factor of T. gondii, was necessary for SOCS1 regulation and escape of IFNγ mediated nitric oxide secretion within macrophages. Surprisingly, when further analyzing Mic8 deficient parasites we noted that inhibition of IFNγ mediated up-regulation of MHC-class II and ICAM1 molecules was independent of cellinvasion. Furthermore, these inhibitory effects were equally observed in type I and II strains of T. gondii and were dependent on excreted and secreted antigens. In contrast, only the virulent RH type I strain additionally induced SOCS1 and efficiently inhibited nitric oxide secretion by IFNγ. The results show that T. gondii makes use of two different mechanisms to escape from IFNγ activity with one mode being straindependent and relying on active cellinvasion and SOCS1 induction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Meissner, Professor Markus
Authors: Stutz, A., Kessler, H., Kaschel, M., Meissner, M., and Dalpke, A.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunobiology
ISSN:0171-2985
ISSN (Online):1878-3279
Published Online:27 August 2011

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