INTERLEUKIN-12 REGULATION BY DR-FIMBRIATED E. COLI

University Of Texas Medical Br Galveston, Galveston TX

Investigators

Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): The mechanism of recurrent urinary tract infection (UTI) and its effect on the kidney function is not well understood. The persistence is a characteristic feature of UTI caused by E. coli that express Dr fimbriae. Uropathogenic E. coli strains bearing Dr fimbriae recognize complement regulatory protein-decay accelerating factor (DAF) as their receptor. Interaction of Dr fimbriae with DAF is associated with cross-linking of receptor, followed by internalization of Dr-positive E. coli into epithelial cells. DAF is a surface protein anchored in the membrane via the glycolipid glycosylphosphatidyllinositol (GPI). Recent findings indicate that cross-linking of complement regulatory proteins on human monocytes/macrophages by certain intracellular pathogens inhibits the production of key immunoregulatory cytokine, interleukin-12 (IL-12). This finding raises the possibility that Dr-positive E. coli may alter cell immune response by downregulating IL-12, followed by impaired production of interferon , a potent stimulator of bactericidal activity of macrophages. The investigators propose to evaluate in three Specific Aims the general hypothesis that cross-linking of DAF on human monocytes/macrophages by E. coli bearing Dr fimbriae inhibits IL-2 production.