Deciphering Host-Pathogen Interactions: Role of Cryptosporidium in Tumorigenesis.

Abstract

Cryptosporidium, a protozoan parasite affecting the gastrointestinal system, is primarily known for causing diarrhea, especially in those with weakened immune systems. However, there is increasingly persuasive evidence that it may be directly involved in tumorigenesis. This review examines some of the potential mechanisms through which Cryptosporidium infections can induce cancer, specifically chronic inflammation, manipulation of the immune system, and alteration of cell signaling pathways. Persistent inflammation with immune system changes due to chronic infection, particularly among immunocompromised hosts, leads to a microenvironment that facilitates tumorigenesis. Cryptosporidium manipulates important cellular pathways such as PI3K, NF-κB, Wnt, and p38/MAPK to promote cell survival, regulate immune responses, and foster tissue remodeling, all of which contribute to a tumor-friendly microenvironment. Moreover, Cryptosporidium virulence factors such as ROP1, sPLA2, and microRNAs disrupt host cellular stability and significantly alter host cellular gene expression, which also exacerbates inflammation and tissue damage. Epidemiological data have indicated higher rates of Cryptosporidium infection in cancer patients, especially patients with gastrointestinal cancers. This, among other observations, raises the possibility that the infection may be connected to cancer progression. In animal models, especially studies with C. parvum-challenged rodents, chronic inflammation, immune repression, and genetic mutations related to neoplasia have been reported. While this has provided us with valuable information, we still have a long way to go to fully understand the long-term ramifications of Cryptosporidium infection. These cover aspects such as the contribution of latent infections and the genetic diversity of Cryptosporidium strains in cancer. Further investigation is urgently needed to understand the molecular processes by which Cryptosporidium might contribute to carcinogenesis and explore potential strategies for therapy and prevention especially among immunocompromised populations.