Analysis of intestinal epithelial cell responses to IFN-γ during <i>Cryptosporidium</i>infection

Abstract Cryptosporidium species are intracellular parasites that infect intestinal epithelial cells (IEC) and the rapid cycle of growth, cell lysis reinfection every 12 hours can cause severe enteric disease in young or immunocompromised patients. Interferon-γ (IFN-γ) has a crucial role protective immunity mice with an IEC-specific deletion IFN-γ receptor (IFN-γR ΔIEC) highly susceptible to infection. However, dynamics signalling IEC how this leads parasite control remain poorly understood. Based on use reporter mouse for IFN vivo, while macrophages showed transient response treatment IFN-γ, exhibited sustained peaks at 24h. Indeed, recombinant transiently limits shedding but takes 24h show activity. Single-cell RNA sequencing enterocytes from naïve infected identified upregulation several IFN-γ-inducible effectors highlighted induction these genes was comparable bystander IEC. Together, results suggest Cryptosporidium-infected responsive signalling, effects may be mediated through activation uninfected enterocytes. These studies provide new insights into function broadly relevant other IEC-restricted pathogens. Supported by grants NIH (R01 AI148249) post-doctoral fellowships Canadian Institutes Health Research Fonds de Recherche du Québec – Santé.