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Type I interferon: the mediator of bacterial infection-induced necroptosis

Cellular & Molecular Immunology volume 10, pages 4–6 (2013)Cite this article

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Innate immune responses are essential for the host to fight against invading microbes. Innate immune receptors or pattern recognition receptors recognize conserved microbial molecules and trigger innate immune responses. Pattern recognition receptors such as Toll-like receptors primarily signal through the adaptor MyD88 to activate NF-κB, while other Toll-like receptors signal via TRIF to activate IRF-3 resulting in the expression of type I interferons (IFNs).1 Type I IFNs play a crucial role in antiviral immune responses but are also important for the host response against bacterial infection.2 Paradoxically, the production of type I IFNs leads to protection against some intracellular pathogens such as Mycobacterium tuberculosis,3 while it enhances the susceptibility to other intracellular pathogens such as Listeria monocytogens.4,5 The mechanisms whereby type I IFN signaling during intracellular bacterial pathogen infection causes differential outcomes remain to be established. In a recent study reported in Nature Immunology, Robinson et al. describe a pathway in which Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits the host type I IFN signaling to kill macrophages through the induction of necroptosis, a specialized pathway of programmed necrosis.6

To evaluate the role of type I IFNs in infection, Robinson et al. challenged mice deficient in the receptor for IFN-α and IFN-β (IFNAR-deficient (Ifnar−/−)) with S. Typhimurium. Improved survival as well as lower bacterial burden in the spleen and liver was observed in Ifnar−/− mice relative to that of the wild-type mice. Furthermore, better protection against S. Typhimurium infection was also obtained via adoptive transfer of Ifnar−/− bone marrow into wild-type or Ifnar−/− hosts, compared with the bone marrow from wild-type mice, indicating that hematopoietic cell-derived type I IFNs play an prominent role in the susceptibility to infection in Ifnar−/− mice.

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Acknowledgements

The authors (QD and JX) were supported by the grants from China Scholarship Council (File No. 2011699033), New Century Excellent Talents in Universities (NCET-11-0703), National Natural Science Foundation of China (81071316, 81271882) and Southwest University (XDJK2009A003, XDJK2011D006, kb2010017).

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Authors and Affiliations

  1. Institute of Modern Biopharmaceuticals, School of Life Science, Southwest University, Chongqing, China

    Qinglin Du & Jianping Xie

  2. Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA

    Ha-Jeong Kim & Xiaojing Ma

  3. Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

    Xiaojing Ma

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Correspondence to Xiaojing Ma.

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Du, Q., Xie, J., Kim, HJ. et al. Type I interferon: the mediator of bacterial infection-induced necroptosis. Cell Mol Immunol 10, 4–6 (2013). https://doi.org/10.1038/cmi.2012.52

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