Cryptosporidium parvum is a zoonotic apicomplexan parasite responsible for a diarrheal disease named cryptosporidiosis. The immature intestinal immune system in very young animals and children under 5 placesthem at high risk of developing severe cryptosporidiosis(Laurent, Lacroix‐Lamandé, Int. J. Parasitol. 2017).In order to identify susceptibility and resistance factors to cryptosporidiosis, we investigated the difference in susceptibility to Cryptosporidium parvum infection in five inbred mouse lines with well‐defined genetics (C57BL/6, BALB/c, CBA, DBA/2 and C3H/HeN). The parasitic load analysis of young mice at the peak of infection allowed us to clearly distinguish sensitivity differences gathered in three groups (BALB/c S+++, C57BL/6 S++, C3H/HeN S+). We next deciphered the mechanisms responsible for this difference by using these three strains of mice and by comparing some physiological and immunological parameters. At this stage, two elements emerge from our first analyzes: a difference in the recruitment of CD11c+ MHCII+ CD64+ Ly6c+ inflammatory monocytes in C3H/HeN mice and a difference in the expression of the antimicrobial peptide, Reg3γ, which is strongly overexpressed after infection in C3H/HeN mice.This project is part of the multi‐partner project APIS‐GENE "Healthycalf" which aims to identify neonatal susceptibility biomarkers in calves.