The enteric protozoan parasite Entamoeba histolytica is the cause of potentially fatal
amebic colitis and
liver abscesses. E. histolytica trophozoites colonize the colon, where they induce
inflammation, penetrate the mucosa, and disrupt the host immune system. The early establishment of E. histolytica in the colon occurs in the presence of antimicrobial human (LL-37) and murine (
CRAMP [
cathelin-related antimicrobial peptide])
cathelicidins, essential components of the mammalian innate defense system in the intestine. Studying this early step in the pathogenesis of
amebic colitis, we demonstrate that E. histolytica trophozoites or their released
proteinases, including
cysteine proteinase 1 (EhCP1), induce intestinal
cathelicidins in human intestinal epithelial cell lines and in a mouse model of
amebic colitis. Despite induction, E. histolytica trophozoites were found to be resistant to killing by these
antimicrobial peptides, and LL-37 and
CRAMP were rapidly cleaved by released amebic
cysteine proteases. The
cathelicidin fragments however, did maintain their antimicrobial activity against bacteria. Degradation of intestinal
cathelicidins is a novel function of E. histolytica
cysteine proteinases in the evasion of the innate immune system in the bowel. Thus, early intestinal epithelial colonization of invasive trophozoites involves a complex interplay in which the ultimate outcome of
infection depends in part on the balance between degradation of
cathelicidins by amebic released
cysteine proteinases and upregulation of proinflammatory mediators which trigger the inflammatory response.