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The PYHIN protein family as mediators of host defenses

Summary:  The innate immune response is the first line of defense against infection and relies on the ability of immune cells to detect the presence of infection through germline‐encoded pattern recognition receptors. These include the Toll‐like receptors, the retinoic acid inducible gene‐like receptors, the nucleotide oligomerization domain‐like receptors, and a number of DNA‐sensing molecules. Members of the PYHIN protein family have recently emerged as sensors of microbial DNA. PYHIN proteins bind microbial DNA and form caspase‐1‐activating inflammasomes (AIM2) or drive type I IFN gene transcription (IFI16). Here, we review these discoveries and highlight the emerging role of the PYHIN protein family in mammalian host defenses.