MyD88 deficiency in podocytes does not change the outcome in experimental glomerulonephritis.

Podocytes, together with glomerular endothelial cells, form the kidney filtration barrier. Loss of podocyte function leads to proteinuria and end-stage renal disease. Podocytes are damaged by various diseases. How they respond to damage-associated molecular patterns is however incompletely understood. MyD88 is the central adaptor protein downstream of Toll-like receptor (TLR) / interleukin-1 (IL-1) signaling and key to the initiation of inflammatory responses. Overall design: Here, we challenged WT and podocyte-specific MyD88 knockout mice (MyD88pko) with experimental glomerulonephritis (GN), nephrotoxic nephritis (NTN). Proteinuria, blood urea nitrogen (BUN) and kidney histology were used as read-outs. Podocyte ultrastructure was imaged by STED and infiltrating cells were quantified by FACS. Transcriptomic changes in podocytes of MyD88pko and WT littermate controls were analyzed under healthy and diseased conditions by bulk RNA-seq.