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Batf3+ CD103+ intestinal dendritic cells are critical players in the innate immune control of Cryptosporidium parvum infection

Abstract : Cryptosporidium parvum infection is a “One Health” threat worldwide that leads to acute diarrhea. The development of cryptosporidiosis is closely related to the immune status of its host, affecting primarily young ruminants, infants and immunocompromised individuals. In recent years, several studies have improved our knowledge on the immune mechanisms responsible for the control of the acute phase of the infection. The functional role of mononuclear phagocytes during cryptosporidiosis has long remained unexplored. We identified CD103+ DCs as a key actor for controlling the acute phase of C. parvum infection in neonatal mice1 while Ly6c+ inflammatory monocytes-macrophages participate to the loss of intestinal integrity2. Recently, CD103- DCs have been described in the intestinal mucosae. To further decipher the role of CD103+ versus CD103- DC subsets, we used mice deficient for the transcription factor Batf3 presenting a large reduction in the number of CD103+ CD11b- DCs in their intestine. This deficiency resulted in an increased susceptibility to C. parvum infection. Batf3-/- neonatal mice express lower level of IFNγ and IDO-1 in the early time of infection3. Repeated administrations of rmIL12 to Batf3-/- neonates previous to C. parvum challenge increased the proportion of CD103+ DCs and resulted in a reduced susceptibility to infection. Analysis of DCs isolated from the intestine of infected WT and Batf3-/- neonatal mice revealed that CD103+ express higher levels of IL12p40 and IL12p35. Altogether, this suggests that CD103+ CD11b- are key cells in the process of protection by favoring IFNγ production in the early time of the infection thank to their ability to produce large amount of functional IL12.
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Submitted on : Thursday, July 29, 2021 - 4:58:41 PM
Last modification on : Thursday, July 29, 2021 - 4:58:42 PM




Junhua Kong, Jing Wu, Le Guan, Ghislaine Hilbert, Serge Delrot, et al.. Batf3+ CD103+ intestinal dendritic cells are critical players in the innate immune control of Cryptosporidium parvum infection. Planta, Springer Verlag, 2021, 253 (4), pp.131. ⟨10.1007/s00425-021-03613-4⟩. ⟨hal-03307918⟩



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