Avian coronavirus IBV-induced activation of the NLRP3-Caspase-1-IL-1β axis in renal collecting ducts contributes to nephropathogenesis.

Avian coronavirus infectious bronchitis virus (IBV) induces severe renal inflammation and urate deposition in chickens, but the underlying mechanisms remain incompletely understood. Here, we used both in vivo chicken infection models and in vitro primary renal epithelial cell cultures and found that IBV activates the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome, leading to the maturation and secretion of IL-1β (interleukin-1 beta). Pharmacological inhibition of NLRP3 in an in vivo chicken model alleviates renal pathology without affecting viral replication, implicating host inflammatory responses in disease progression. These findings indicate that host inflammasome activation, rather than direct viral replication or cytotoxicity, plays a central role in IBV-associated renal pathology. Notably, we observed that NLRP3 is predominantly expressed in the renal collecting duct, primarily within AQP2 (Aquaporin-2)-positive epithelial cells-an anatomic localization of inflammasome activity not previously reported. Single-cell transcriptomic profiling further revealed that IBV infection reprograms collecting duct cells from an electrolyte-regulating phenotype into a pro-inflammatory state, accompanied by disrupted urate metabolism and impaired ion transport. These findings identify collecting duct-targeted NLRP3 activation as a central mechanism of IBV-induced nephropathy and provide a theoretical foundation for developing targeted anti-inflammatory therapies. IMPORTANCE: In vivo studies in chickens demonstrate that the activation of the NLRP3 inflammasome is a key driver of renal injury during infectious bronchitis virus (IBV) infection. Pharmacological inhibition of NLRP3 significantly alleviates renal inflammation and tissue damage without affecting viral replication, highlighting the central role of host inflammatory responses in disease progression. Importantly, we report for the first time that NLRP3 activation is predominantly localized to AQP2-positive collecting ducts, a nephron segment essential for uric acid excretion and electrolyte balance. IBV infection reprograms these epithelial cells into a pro-inflammatory, metabolically dysregulated state, promoting urate crystal formation and amplifying tissue injury. These findings reveal a spatially confined epithelial-immune axis of coronavirus-induced renal pathology and suggest new avenues for targeted intervention.