Characterization of intestinal macrophages and dendritic cell subsets in neonatal lambs at homeostasis and following Cryptosporidium parvum infection

International audience; Cryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, Cryptosporidium parvum (Cp), with a high prevalence in livestock (cattle, sheep, goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and in particular of CD11c+CD103+CD11b-conventional dendritic cells (cDC) among mononuclear phagocytes (MP) in controlling the acute phase of Cp infection. During infection, in response to chemokine production by infected epithelial cells, newly recruited cDCs produce IL12 and IFNγ contributing to the elimination of the parasite. According to the well-established mouse cDC classification, this Batf3+DC subpopulation corresponds to the cDC1 subset. The aim of this project was to better characterize intestinal MP subpopulations in neonatal lamb and calf at homeostasis and during Cp infection. As in the mouse model, the parasite invades and multiplies mainly in the ileum of animals. However, a peculiarity of young ruminants is the presence of a large ileal Peyer’s patch (lymphoid tissue) that extends all along the ileum. MP were therefore analyzed in lymphoid and non-lymphoid intestinal tissues of lambs and claves. We performed phenotypic and functional analyses of mononuclear phagocytes by flow cytometry and by transcriptomic methods (FLUIDIGM®) respectively, in the distal jejunum, jejunal and ileal Peyer’s patches. We characterized a population of macrophages and three subpopulations of cDC. We demonstrated that the subset identified as cDC1, according to the current common classification of cDC in different species (human, mouse, pig, sheep and chicken), increases with the age of animal. This might be linked with the decrease in sensitivity to C. parvum observed with the age. We are currently investigating the evolution of cDC1 subset during C. parvum infection.