Cryptosporidial Infection Suppresses Intestinal Epithelial Cell MAPK Signaling Impairing Host Anti-Parasitic Defense

Abstract

<i>Cryptosporidium</i> is a genus of <i>protozoan parasites</i> that infect the gastrointestinal epithelium of a variety of vertebrate hosts. Intestinal epithelial cells are the first line of defense and play a critical role in orchestrating host immunity against <i>Cryptosporidium</i> infection. To counteract host defense response, <i>Cryptosporidium</i> has developed strategies of immune evasion to promote parasitic replication and survival within epithelial cells, but the underlying mechanisms are largely unclear. Using various models of intestinal cryptosporidiosis, we found that <i>Cryptosporidium</i> infection caused suppression of mitogen-activated protein kinase (MAPK) signaling in infected murine intestinal epithelial cells. Whereas expression levels of most genes encoding the key components of the MAPK signaling pathway were not changed in infected intestinal epithelial cells, we detected a significant downregulation of <i>p38</i>/<i>Mapk</i>, MAP kinase-activated protein kinase 2 (<i>Mk2</i>), and <i>Mk3</i> genes in infected host cells. Suppression of MAPK signaling was associated with an impaired intestinal epithelial defense against <i>C. parvum</i> infection. Our data suggest that cryptosporidial infection may suppress intestinal epithelial cell MAPK signaling associated with the evasion of host antimicrobial defense.