C5aR1 promotes acute pyelonephritis induced by uropathogenic E. coli

Area of Science:

• Immunology
• Microbiology
• Nephrology

Background:

• C5a receptor 1 (C5aR1), a G protein-coupled receptor, is expressed on both myeloid and epithelial cells.
• C5aR1 binds C5a and is an N-linked glycosylated protein.

Purpose of the Study:

• To investigate the role of C5aR1 in bacterial adhesion and colonization of the renal tubular epithelium.
• To elucidate the mechanisms underlying C5aR1's role in kidney infections.

Main Methods:

• Utilized mouse models with genetic deletion or pharmacologic inhibition of C5aR1.
• Inoculated mice with uropathogenic E. coli (UPEC) via bladder instillation.
• Employed confocal microscopy to visualize bacterial binding.
• Conducted in vitro analyses of renal tubular epithelial cells.

Main Results:

• Genetic deletion or pharmacologic inhibition of C5aR1 significantly reduced acute kidney infection in mice.
• Reduced expression of terminal α-mannosyl residues (Man), a UPEC type 1 fimbriae ligand, was observed on renal tubular epithelium.
• C5a stimulation in vitro enhanced Man expression and subsequent bacterial adhesion, partly mediated by TNF-α via C5aR1 signaling.

Conclusions:

• C5aR1 has a previously unrecognized pathogenic role in acute pyelonephritis.
• C5a/C5aR1 signaling upregulates carbohydrate ligands on renal tubules, facilitating UPEC adhesion.