A Giardia Cathepsin‐B‐like Protease Cleaves Interleukin‐8 From Intestinal Epithelial Cells

Abstract

Interleukin‐8 (CXCL8) secretion from intestinal epithelial cells is an early event in acute intestinal inflammation. Infection with the non‐invasive, small intestinal protozoan parasite Giardia duodenalis rarely results in overt intestinal inflammation.ObjectiveTo determine if Giardia trophozoites modulate CXCL8 secretion from ex vivo human small intestinal biopsies or in vitro Caco‐2 monolayers administered interleukin (IL)‐1β or Salmonella typhimurium, and identify mechanisms involved.ResultsCo‐incubation of ex vivo human small intestinal biopsies or in vitro Caco‐2 monolayers with Giardia trophozoites significantly reduced supernatant levels of CXCL8 following stimulation with IL‐1β or S. typhimurium and involved parasite‐mediated cleavage of CXCL8. Giardia trophozoites secreted three cysteine proteases, one sensitive to the cathepsin‐B inhibitor Ca‐074Me. Inhibition of Giardia‐secreted cysteine proteases with a cysteine protease inhibitor (E‐64d) or Ca‐074Me prevented cleavage of CXCL8.ConclusionGiardia trophozoites secrete a cathepsin‐B‐like protease that cleaves CXCL8. Funding provided by NSERC, AIHS, and CCFC.