Dual transcriptomics to decipher the interferon-gamma independent responses to intestinal Cryptosporidium parvum infection.

Abstract

Abstract Background: This study characterizes the IFNγ independent host immune response against C. parvum to discover new targets to halt the disease. We used transcriptomic analysis of ileum and cecum intestinal sections of IFNγ-deleted mice that were treated with Soluble Toxoplasma gondii antigen (STAg) or PBS upon C. parvum infection. Results: STAg treatment reduced the oocyst shedding in C. parvum infected IFNγ deleted mice. To understand the IFNγ independent mechanism of STAg treatment against C. parvum, we performed 12 RNAseq comparisons between tissues, treatments, and infection status for Mus musculus and C. parvum. In the ileum, regardless of STAg or PBS treatment, more than 100 genes had a significant differential expression. Within STAg treated mice, a total of 129 genes for ileum and 78 for the cecum were classified as differentially expressed. We found in high abundance at least 28 genes related to IFN type I response in infected mice treated with STAg, among them, the oligoadenylate synthetase and Schlafen family gene members. For C. parvum transcriptome analysis, we observed in the ileum high abundance of the oocyst wall protein 1 and some mucins; while in the cecum, the RRM domain containing-protein and Tryptophan synthase beta chain transcripts were the more abundant transcripts. Conclusions: STAg treatment and C. parvum infection induced a type I interferon response that would be the cause of the reduction of oocyst shedding in STAG treated mice in an IFNy independent manner. While the depth of sequence did not allow us to observe in detail differential expression of genes in C. parvum, we found differences in parasite gene expression between the ileum and the cecum.