Targeting innate immunity during the neonatal period with NOD2-based ligands to fight Cryptosporidiosis

National audienceDuring the neonatal period, the immune system is still immature, giving at newborns susceptibility to infections such as Cryptosporidiosis, caused by the parasite Cryptosporidium parvum (C. parvum). This zoonosis is due to an orally transmitted protozoan that develops in intestinal epithelial cells and causes acute diarrhea in very young ruminants. Cryptosporidiosis also causes a moderate-to-severe diarrhea in children under 5 years and immune-compromised hosts. Today, there is no vaccine to prevent infection nor efficient treatment, and there is therefore an urgent need for the development of new methods to control this zoonosis. The innate immunity has been shown to play an important role in the control of C. parvum infection (Lacroix-Lamandé & Laurent, 2017). We hypothesize that modulation of the innate immune system during the neonatal period could enhance the immune defense at young ages and favor the control of cryptosporidiosis. We have previously shown that the immunostimulation with ligands of the innate immunity targeting the Toll Like Receptors (TLRs) can help the mice to control C. parvum infection. (Barrier et al., 2006 ; Lacroix-Lamandé et al. 2009 ; Lantier et al., 2014 ; Lacroix-Lamandé et al., 2014). Nucleotides Oligomerization Domain (NODs) are other innate immune receptors expressed by diverse immune cells (monocytes, dendritic cells, eosinophils, and neutrophils) and by epithelial cells. They recognize peptidoglycan of bacteria. In the intestine, these receptors are present on the different types of intestinal epithelial cells (enterocytes, Paneth cells and Goblet cells) and are essential in the maintenance of intestinal homeostasis. In this work, we studied if, during the neonatal period, the stimulation of these NOD receptors could efficiently stimulate the innate immune responses and confer protection against an enteric infection by C. parvum