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International audience; Cryptosporidiosis is a poorly controlled zoonosis caused by the intestinal infection by a protozoan parasite, Cryptosporidium parvum (Cp), presenting a high prevalence in ruminant farms (cattle, sheep, goats). Young animals with an immature intestinal immune system are particularly susceptible to this infection. In a neonatal mouse model, we previously demonstrated the key role of innate immunity and in particular of CD11c+CD103+CD11b- dendritic cell (DC) subset incontrolling the acute phase of Cp infection [1]. During infection, in response to chemokine production by infected epithelial cells, newly recruited CD11c+CD103+CD11b- DC produce IL12 and IFNγ contributing to the elimination process of the parasite. According to the current common classification of DC in different species (human, mouse, pig, sheep, and chicken), this subpopulation can be identified as the cDC1 subset of conventional DC. The aim of this project was to better characterize intestinal DC subpopulations in lamb and to determine their role during Cp infection. As in the mouse model, the parasite invades and multiplies mainly in the ileum of young lambs. However, a peculiarity of young ruminants is the presence of a large ileal Peyer’s patch (lymphoid tissue) that extends all along the ileum. We characterized in various compartments of the lamb small intestine (lymphoid and non-lymphoid) the various mononuclear phagocyte populations by performing a phenotypic and functional analysis by flow cytometry and transcriptomic methods respectively. We followed the evolution of the cell subsets according to the age of the animals and during Cp infection. This work represents the first fine description of mononuclear phagocyte cell subsets in the small intestine of young lambs at homeostasis and during the course of C. parvum infection.

National audience; Numerous studies recently describe the relationship between influences during early-life period and later-life health and disease. Cryptosporidium parvum is a zoonotic parasite responsible for a diarrheal disease that affects mostly children under 5 and immunocompromised patients (AIDS or organ transplant patients). Epidemiological studies have reported that after resolution of C. parvum infection, patients still suffer for abdominal pain. In this context, by using a neonatal mouse model of cryptosporidiosis, we tried to decipher the intestinal consequences at adulthood of the neonatal infection by analyzing the composition of the microbiota, the composition of immune cells in the intestine but also consequences on visceral sensitivity and the susceptibility to an unrelated intestinal infection. We observed that adult mice infected by C. parvum during the neonatal period display a modification of microbiota and of the composition of immune cells. These intestinal modifications were associated with an increased viscero-sensitivity and with a higher sensitivity to Salmonella infection. Altogether these results clearly demonstrate that an infection by C. parvum during the neonatal period induces intestinal imprinting that can be responsible for abdominal pains and increased susceptibility to another intestinal infection, way after the resolution of C. 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.