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

Abstract

Cryptosporidium is a genus of protozoan parasites 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 Cryptosporidium infection. To counteract host defense response, Cryptosporidium 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 Cryptosporidium 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 p38/Mapk, MAP kinase-activated protein kinase 2 (Mk2), and Mk3 genes in infected host cells. Suppression of MAPK signaling was associated with an impaired intestinal epithelial defense against C. parvum infection. Our data suggest that cryptosporidial infection may suppress intestinal epithelial cell MAPK signaling associated with the evasion of host antimicrobial defense.

Genomic Analysis of Gastrointestinal Parasite Resistance in Akkaraman Sheep

“…Alternatively, ALK and SCG2 genes were also identified as being associated with the mitogen-activated protein kinase (MAPK) signaling pathway, where both genes are involved in the positive regulation of said cascade (GO:0043410 and GO:0000165, respectively). It has been reported that MAPK signaling is suppressed in host intestinal epithelial cells in an infection caused by Cryptosporidium , which is a protozoan parasite that infects intestinal epithelial cells similar to the Eimeria species [ 63 ]. Along with apoptotic and MAPK pathways, SCG2 has been determined to play a very active role in the formation of innate immune and adaptive immune responses in the body.…”

Gene expression profile of HCT-8 cells following single or co-infections with Cryptosporidium parvum and bovine coronavirus

“…However, a signi cant downregulation of p38/Mapk, MAP kinase-activated protein kinase 2 (Mk2), and Mk3 genes was found. This suppression of MAPK signalling activity in C. parvum-infected intestinal epithelial cells was postulated as a strategy to evade host immune response [50].…”

Is Cryptosporidium a hijacker able to drive cancer cell proliferation?

“…Moreover, a significant downregulation of p38/MAPK, MAP kinase-activated protein kinase 2 (Mk2), and Mk3 genes was found in an in vitro model of cryptosporidiosis ( He et al, 2021 ). Suppression of MAPK signaling was linked with an impaired intestinal epithelial defense against C. parvum infection ( He et al, 2021 ) ( He et al, 2021 ). Interestingly, p38/MAPK has described as a tumor suppressor ( Bulavin and Fornace, 2004 ).…”