CRYPTOSPORIDIUM-PARVUM INFECTION OF HUMAN INTESTINAL EPITHELIAL-CELLSINDUCES THE POLARIZED SECRETION OF C-X-C CHEMOKINES

Cryptosporidium parvum infects intestinal epithelial cells and does no t invade deeper layers of the intestinal mucosa. Nonetheless, an infla mmatory cell infiltrate that consists of neutrophils and mononuclear c ells is often present in the lamina propria, which underlies the epith elium. This study investigated the host epithelial cell response to C. parvum by assessing in vitro and in vivo the expression and productio n of proinflammatory cytokines by intestinal epithelial cells after in fection. The human colon epithelial cell lines HCT-I and Caco-2 and hu man intestinal xenografts in SCID mice mere infected with C. parvum. T he expression and secretion of the C-S-C chemokines interleukin-8 (IL- 8) and GRO alpha were determined by reverse transcription-PCR analysis and enzyme-linked immunosorbent assay. Our results demonstrate that u pregulated expression and secretion of IL-8 and GRO alpha after C. par vum infection of intestinal epithelial cells first occurred 16 to 24 h after infection and increased over the ensuing 1 to 2 days, The kinet ics of C-X-C chemokine production by C. parvum-infected epithelial cel ls contrast markedly with the rapid but transient expression of C-X-C chemokines by epithelial cells infected with invasive enteric bacteria . C-X-C chemokine secretion in C. parvum-infected epithelial cells occ urred predominantly from the basolateral surface in polarized monolaye rs of Caco-2 cells grown in Transwell cultures, whereas cell lysis occ urred at the apical surface. The basolateral secretion of IL-g and GRO alpha from C. parvum-infected epithelial cells suggests that C-X-C ch emokines produced by those cells contribute to the mucosal inflammator y cell infiltrate in the underlying intestinal mucosa.