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Metallothionein differentially affects the host response to Listeria infection both with and without an additional stress from cold-restraint

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Cell Stress and Chaperones Aims and scope

Abstract

Acute stress alters anti-bacterial defenses, but the neuroimmunological mechanisms underlying this association are not yet well understood. Metallothionein (MT), a cysteine-rich protein, is a stress response protein that is induced by a variety of chemical, biological, and psychological stressors, and MT has been shown to influence immune activities. We investigated MT’s role in the management of anti-bacterial responses that occur during stress, using a C57BL/6 (B6) strain that has targeted disruptions of the Mt1 and Mt2 genes (B6-MTKO), and a B6 strain that has additional copies of Mt (B6-MTTGN). The well-characterized listeriosis model was used to examine immune mechanisms that are altered by a 1-h stress treatment (cold-restraint, CR) administered just prior to bacterial infection. Intriguingly, MT gene doses both greater and lower than that of wild-type (WT) B6 mice were associated with improved host defenses against Listeria monocytogenes (LM). This augmented protection was diminished by CR stress in the MTKO mice, but transgenic mice with additional MT copies had no CR stress-induced increase in their listerial burden. During the transition from innate to adaptive immunity, on day 3 after infection, oxidative burst and apoptosis were assessed by flow cytometric methods, and cytokine transcription was measured by real-time quantitative PCR. MT gene expression and CR-stress affected the expression of IL-6 and TNFα. Additionally, these genetic and environmental modulations altered the generation of ROS responses as well as the number of apoptotic cells in livers and spleens. Although the level of MT altered the listerial response, MT expression was equally elevated by listerial infection with or without CR stress. These results indicate the ability of MT to regulate immune response mechanisms and demonstrate that increased amounts of MT can eliminate the immunosuppression induced by CR.

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Acknowledgments

This work was supported, in part, by U01 ES016014 (DAL) and R01 ES007408 (MAL).

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  1. Rebecca T. Emeny

    Present address: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, GmbH, Ingolstädter Landstraße 1, D-85764, Neuherberg, Germany

Authors and Affiliations

  1. Laboratory of Immunology, Wadsworth Center, New York State Department of Health, 150 New Scotland Ave, Albany, NY, 12201, USA

    Rebecca T. Emeny, Jane Kasten-Jolly, Tapan Mondal & David A. Lawrence

  2. Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, 06269, USA

    Michael A. Lynes

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  1. Rebecca T. Emeny
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  2. Jane Kasten-Jolly
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  5. David A. Lawrence
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Correspondence to David A. Lawrence.

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Emeny, R.T., Kasten-Jolly, J., Mondal, T. et al. Metallothionein differentially affects the host response to Listeria infection both with and without an additional stress from cold-restraint. Cell Stress and Chaperones 20, 1013–1022 (2015). https://doi.org/10.1007/s12192-015-0630-z

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  • DOI: https://doi.org/10.1007/s12192-015-0630-z

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