Dual transcriptomics to determine interferon-gamma independent host response to intestinal Cryptosporidium parvum infection

Abstract

Background: Protective immune responses to Cryptosporidium parvum, a zoonotic, gastrointestinal parasite, are primarily dependent on the presence of interferon-gamma (IFNγ). We discovered that treatment with soluble T. gondii antigen (STAg) reduces Cryptosporidium parvum shedding in the absence of IFNγ. To identify the protective IFNγ independent responses elicited by STAg, we conducted a transcriptomic analysis of intestinal sections of IFNγ-deleted, C. parvum infected or uninfected mice treated with STAg or PBS. Results: STAg treatment reduced oocyst shedding in C. parvum infected IFNγ deleted mice. Gene ontology analysis of the intestinal transcriptomes suggested that both C. parvum infection and STAg treatment changes the transcript abundance of genes involved in the host cell membrane, intracellular and extracellular transport, and immune responses. We found in high abundance 37 genes related to IFN type I response in infected mice treated with STAg. Among these genes, members of the oligoadenylate synthetase and Schlafen family were identified. Conclusions: STAg treatment of C. parvum infected mice induced both host immune and metabolism changes associated with a reduction in shedding. Several components of the type I interferon immune response were more abundant in the ileum of C. parvum infected in IFNγ-deleted mice. Future studies will explore the role of type I IFN mediated immune responses in controlling C. parvum infections. STAg treatment appears to only affects the host transcriptome while the parasite transcriptome remains unaffected. Several C. parvum genes, including mucin genes, are more abundant during infection of animals, which opens new avenues in C. parvum research.