Type I interferon receptor signalling as a master switch for the negative regulation of cytokine networks.

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Viral infections are controlled by the induction of an innate immune response. As a first line of defense, a set of cytokines known as type I interferons (IFNs) are produced by cells after they sense the presence of viruses. These type I IFNs include IFN-alpha and IFN-beta and are detected by cells expressing the IFN a/ß receptor (IFNAR). Signalling through the IFNAR causes multiple changes inside cells that facilitate the clearance of viruses. In some cases, this response results in excessive production of cytokines, leading to a so-called cytokine storm that can be very toxic. This is a cause of mortality in cases of severe acute respiratory syndrome (SARS) and infection with some strains of influenza, for example. This phenomenon is not limited to viruses. Bacteria are responsible for toxic shock syndrome in women. The same mechanisms underlying cytokine storms may also contribute to less toxic responses that nevertheless cause unwanted side effects, such as during overly robust inflammation.