A cilia-dependent inflammatory programme links bacterial detection to kidney disease

作者：Amandine Aka, Joran Martin, Fanny Kopp, Teresa Bulfone, Samuel Chauvin, Camille Cohen, Martine Burtin, E. Wolfgang Kuehn, Anne-Sophie Dangeard, Maryse Moya-Nilges, Nicolas Cagnard, Nicolas Goudin, Meriem Garfa-Traoré, Marceau Quatredeniers, Cong Xu, Laurent Audry, Jost Enninga, Matthieu Rousseau, Cécile Arrieumerlou, Jieqing Fan, Sophie Saunier, Fabiola Terzi, Molly A. Ingersoll, Henri Lichenstein, Amandine Viau, Frank Bienaimé · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.04.24.720658 · 研究领域：Genetic and Kidney Cyst Diseases、Cerebrospinal fluid and hydrocephalus、Biomedical Research and Pathophysiology

ABSTRACT The primary cilium is a microtubule-based sensory organelle projecting from the plasma membrane of most mammalian cells. Genetic defects in ciliary components cause chronic kidney disease (CKD) characterized by heightened production of inflammatory and fibrogenic mediators by tubular epithelial cells. Yet, whether this reflects a physiological role of the primary cilium remains unknown. Here, we show that primary cilia on kidney tubular cells bind uropathogenic Escherichia coli and, in response to bacterial components, initiate a fibro-inflammatory program reminiscent of CKD. Integrating single-cell transcriptomics with conditional mouse models, we observed that epithelial cilia orchestrate a similar fibro-inflammatory response in the absence of infection during CKD. This convergence reveals a shared cilia-dependent signalling axis governing both host–pathogen responses and CKD progression. Mechanistically, cilia ablation selectively impairs tubular responses to ADP-heptose, a pathogen-associated molecular pattern that activates NF-κB via the cytosolic innate immune receptor ALPK1. In human kidney organoids, ADP-heptose induces robust fibro-inflammation, and genetic or pharmacological inhibition of ALPK1 attenuates this response in a rodent CKD model. Together, these findings identify primary cilia as central orchestrators of a fibro-inflammatory program linking pathogen detection to kidney disease progression.