ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways

The interferon (IFN)–inducible protein Z-DNA binding protein 1 [ZBP1; also known as DNA-dependent activator of IFN regulatory factors (DAI) and DLM-1] was identified as a double-stranded DNA sensor, which instigates innate immune responses. However, this classification has been disputed, and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptorinteracting protein kinase 1 (RIPK1)–RIPK3–caspase-8 axis. ZBP1 regulates NLRP3 (nucleotide and oligomerization domain, leucine-rich repeat–containing protein family, pyrin domain containing 3) inflammasome activation as well as induction of apoptosis, necroptosis, and pyroptosis in IAV-infected cells. ZBP1 deficiency protected mice from mortality during IAV infection owing to reduced inflammatory responses and epithelial damage. Overall, these findings indicate that ZBP1 is an innate immune sensor of IAV and highlight its importance in the pathogenesis of IAV infection.T.-D.K. is supported by the U.S. NIH (AI101935, AI124346, AR056296, and CA163507) and the American Lebanese Syrian Associated Charities; S.M.M. is supported by the National Health and Medical Research Council of Australia R.G. Menzies Early Career Fellowship

Chronic Unilateral Uveitis with Macular Edema Secondary to Dabrafenib for Pilocytic Astrocytoma

This report describes a unique case of chronic unilateral anterior uveitis associated with macular edema while on oral dabrafenib treatment for chronic recurrent pilocytic astrocytoma. After gradual taper of prednisolone acetate OS, the patient developed recurrent mild low-grade anterior uveitis and macular edema OS that required low dose of prednisolone acetate OS to prevent recurrences while on oral dabrafenib. When oral dabrafenib was temporarily discontinued for 3 months due to her ocular inflammation, she had no flares of her uveitis; however, her tumor increased significantly in size. The collaborative decision was made to continue her oral dabrafenib while on topical anti-inflammatory therapy for her uveitis. Clinicians should be aware of this potential unilateral sequela of uveitis secondary to dabrafenib. Further investigation should be conducted to identify factors that may place certain patients at higher risk for this complication. © 2021 The Author(s). Published by S. Karger AG, Basel.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]