Abstract: TH-PO0236
Primary Cilia Couple Host-Pathogen Sensing to CKD Progression
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Aka, Amandine, INSERM U1151, Institut Necker Enfants Malades, Paris, France
- Martin, Joran, Institut IMAGINE, INSERM U1163, Paris, France
- Cohen, Camille, INSERM U1149, Centre de recherche sur l'inflammation, Paris, France
- Rousseau, Matthieu, Mucosal Inflammation and Immunity Team, Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Arrieumerlou, Cécile, Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Fan, Jieqing, Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China
- Saunier, Sophie, Institut IMAGINE, INSERM U1163, Paris, France
- Terzi, Fabiola, INSERM U1151, Institut Necker Enfants Malades, Paris, France
- Ingersoll, Molly, Mucosal Inflammation and Immunity Team, Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Lichenstein, Henri, Drug Farm USA LLC, Albany, New York, United States
- Viau, Amandine, Institut IMAGINE, INSERM U1163, Paris, France
- Bienaime, Frank, INSERM U1151, Institut Necker Enfants Malades, Paris, France
Background
The infiltration of the kidney by immune cells depends on cytokines induced by the activation of innate immunity receptors that recognize molecular pattern released from pathogens (PAMP) or damaged cells (DAMP). The ensuing inflammatory response leads to the elimination of the pathogen and tissue repair, but it can also promote acute or chronic damage. Common pathologies such as pyelonephritis or obstruction illustrate these processes, combining inflammation and fibrosis. However, the mechanisms by which kidney tubular cells integrate these mechanical and chemical signals remain partially unsolved.
Acting as a signaling hub regulating kidney homeostasis, the primary cilia of tubular cells project into the lumen, where they are subjected to deflection by urinary flow. We recently demonstrated that the primary cilia from tubular cells drive immune cell recruitment into the kidney in genetic chronic kidney disease (CKD).
We now hypothesize that the primary cilia could be a PAMP/DAMP sensor.
Methods
We generated cilia-deficient tubular cells and mice models and subjected them to either infection with Escherichia coli (UPEC) uropathogenic bacteria or obstruction. Kidney lesions and fibrosis were quantified on PAS and Picrosirius-stained kidney sections. Quantitative PCR assessed tubular dedifferentiation, inflammation and fibrosis. Primary cilia binding and immune cell recruitment were measured by immunohistochemistry.
Results
We showed that primary cilia on kidney tubular cells bind UPEC and initiate a fibro-inflammatory programme reminiscent of CKD. We demonstrated that pyelonephritis and ureteral obstruction, both known to induced PAMP/DAMP, trigger similar cilia elongation and genetic CKD-related cytokines resulting in fibro-inflammation in mouse models. Genetic cilia ablation of kidney tubular cells reduces the fibro-inflammatory response triggered by obstruction or infection in vitro and in vivo. Mechanistically, cilia ablation selectively disrupts tubular responses to ADP-heptose, a PAMP that activates NF-κB through the cytosolic receptor ALPK1. Pharmacological inhibition of this pathway drastically reduced the cilia-dependent inflammatory response.
Conclusion
These findings identify primary cilia as central organisers of a unifying fibro-inflammatory programme linking host–pathogen detection to CKD progression.
Acknowledgment
We thank the members of the LEAT, histology, genomics, bioinformatics, cell imaging and image analysis facilities (S.F.R Necker INSERM US24, Paris, France), the mouse renal physiology facility (Cordeliers Research Center, Paris, France), and the Ultrastructural BioImaging Core Facility (Institut Pasteur, Paris, France) for technical assistance.
Funding
- Government Support – Non-U.S.