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Transcriptional response of human microglial cells to interferon-γ

Genes & Immunity volume 6, pages 712–719 (2005)Cite this article

Abstract

Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-γ, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-γ treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-γ signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-γ induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia–T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-γ—a key to understanding cell-mediated immunity of the CNS.

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Acknowledgements

Special thanks to Aaron Becker and Jill Plumb-Smith at the Biomedical Genomic Center, University of Minnesota; Genya Gekker and Wen S Sheng at the Minneapolis Medical Research Foundation; and Wayne Xu at the Supercomputing Institute, University of Minnesota. The Kapur laboratory is supported, in-part, by research grants from the NIH, USDA, NSF, and DHS. BR and BM are supported by the Neurobehavior/Neuroimmune Addiction Research training program at the University of Minnesota funded by the National Institute on Drug Abuse, NIDA T32 DA07097. This work was supported in part by US Public Health Service Grant DA04381.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, USA

    R B Rock, S Hu, C A Baker & P K Peterson

  2. Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, University of Minnesota, Minneapolis, MN, USA

    R B Rock, S Hu, C A Baker & P K Peterson

  3. Biomedical Genomic Center, University of Minnesota, Minneapolis, MN, USA

    A Deshpande, S Munir, B J May & V Kapur

  4. Department of Microbiology, University of Minnesota, Minneapolis, MN, USA

    S Munir, B J May & V Kapur

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  1. R B Rock
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Correspondence to V Kapur.

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Disclosures

Human fetal brain tissue was obtained under protocol approved by the Human Subjects Research Committee at our institution.

None of the authors has a commercial or other association that might pose a conflict of interest with the current study.

Presented at the Society of Neuroimmune Pharmacology Annual Meeting, April 2004, Santa Fe, New Mexico.

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Rock, R., Hu, S., Deshpande, A. et al. Transcriptional response of human microglial cells to interferon-γ. Genes Immun 6, 712–719 (2005). https://doi.org/10.1038/sj.gene.6364246

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