Recent　work　in　a　murine　model　of　ascending　urinary　tract　infection　has　suggested　that　C5a/C5aR1　interactions　play　a　pathogenic　role　in　the　development　of　renal　infection　through　enhancement　of　bacterial　adhesion/colonization　to　renal　tubular　epithelial　cells　(RTECs).　In　the　present　study,　we　extended　these　observations　to　human.　We　show　that　renal　tubular　epithelial　C5aR1　signaling　is　involved　in　promoting　uropathogenic　Escherichia　coil　(UPEC)　adhesion/invasion　of　host　cells.　Stimulation　of　primary　cultures　of　RTEC　with　C5a　resulted　in　significant　increases　in　UPEC　adhesion/invasion　of　the　RTEC.　This　was　associated　with　enhanced　expression　of　terminal　oc-mannosyl　residues　(Man)　(a　ligand　for　type　1　fimbriae　of　E.　cols)　in　the　RTEC　following　C5a　stimulation.　Mechanism　studies　revealed　that　C5aR1-mediated　activation　of　ERK1/2/NF-kappa　B　and　upregulation　of　proinflammatory　cytokine　production　(i.e.,　INF-alpha)　is　at　least　partly　responsible　for　the　upregulation　of　Man　expression　and　bacterial　adhesion.　Clinical　sample　studies　showed　that　C5aR1　and　Man　were　clearly　detected　in　the　renal　tubular　epithelium　of　normal　human　kidney　biopsies,　and　UPEC　bound　to　the　epithelium　in　a　D-mannose-dependent　manner.　Additionally,　C5a　levels　were　significantly　increased　in　urine　of　urinary　tract　infection　patients　compared　with　healthy　controls.　Our　data　therefore　demonstrate　that,　in　agreement　with　observations　in　mice,　human　renal　tubular　epithelial　C5aR1　signaling　can　upregulate　Man　expression　in　RTEC,　which　enhances　UPEC　adhesion　to　and　invasion　of　RTEC.　It　also　suggests　the　in　vivo　relevance　of　upregulation　of　Man　expression　in　renal　tubular　epithelium　by　C5a/C5aR1　interactions　and　its　potential　impact　on　renal　infection.