Protozoan parasites, such as Plasmodium, Leishmania, Toxoplasma, Cryptosporidium, and Trypanosoma, are causative agents of health-threatening diseases in both humans and animals, leading to significant health risks and socioeconomic losses globally. The development of effective therapeutic and prevention strategies for protozoan-caused diseases requires a full understanding of the pathogenesis and protective events occurring in infected hosts. Interferons (IFNs) are a family of cytokines with diverse biological effects in host antimicrobial defense and disease pathogenesis, including protozoan parasite infection. Type II IFN (IFN-γ) has been widely recognized as the essential defense cytokine in intracellular protozoan parasite infection, whereas recent studies also revealed the production and distinct function of type I and III IFNs in host defense against these parasites. Decoding the complex network of the IFN family in host–parasite interaction is critical for exploring potential new therapeutic strategies against intracellular protozoan parasite infection. Here, we review the complex effects of IFNs on the host defense against intracellular protozoan parasites and the crosstalk between distinct types of IFN signaling during infections.

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.