Function of intestinal mononuclear phagocyte in the control of neonatal enteric disease: innate response to Cryptosporidium parvum
Résumé
At birth, the immune system of a newborn is still in development making them more susceptible to infection. Before they establish specific immune responses, neonates are protected by a development of maternally transmitted immunity and by innate immune responses they develop. To study the innate immune responses during an enteric infection a Cryptosporidium parvum mouse model was used. The development of this zoonotic protozoan parasite (which affects only immunodeficient individuals and new-horns) is restricted to the intestinal epithelium. Using T and B cell deficient animals the efficient control of the parasite was observed demonstrating the importance of innate mechanisms in the control of infection. The established importance of IL-12 in the control of the parasite development, the weak colonisation of CD 11 c+ cells in the neonate mucosa at homeostasis and their important recruitment during infection, leads us to make the hypothesis that this cell population plays a major role in the innate immune response. A transgenic mouse model allowed for a conditional depletion of CD 11 c+ cells showed their absence favoured the parasite development in newborn and makes normally resistant adult mice sensitive to the infection. These results demonstrate the crucial role of CD 11 c+ cells in the control of an established infection and also in the early stages of parasite development. In the intestinal mucosa co-exist different populations of mononuclear phagocyte which express markers allowing to distinguish two populations originating from different precursors of CDllc+ cells, one resident (CD11c+ CX3CR1+) and the other with migratory properties (CD11c+ CD103+). Following CDllc+ cell depletion, both subsets are eliminated from the intestinal mucosa and among mononuclear phagocytes only remaining F4/80+ macrophages mainly within the muscularis mucosae. Studies are underway to investigate the functional properties of the different CD 11 c+ subsets and their implication in the control of the C.parvum infection.