Dendritic cells play a role in host susceptibility to Cryptosporidium parvum infection

•Depletion of DCs in vivo increases susceptibility to Cryptosporidium parvum infection.•Adoptive transfer of stimulated DCs reduces C. parvum infection levels.•Reduction in infection correlates to an increase in IFN-γ in T cell.•DCs pulsed with sporozoites and co-cultured with CD4+ and CD8+ T cells produced higher IFN-γ levels.

Our previous studies have described dendritic cells (DCs) to be important sources of Th1 cytokines such as IL-12 and IL-2 in vitro, following stimulation with Cryptosporidium parvum antigens. We further established the role of DCs during cryptosporidiosis using a diphtheria toxin promoter regulated transgenic CD11c-DTR/EGFP mouse model. In vivo depletion of CD11c+ cells in CD11c-DTR-Tg mice significantly increased susceptibility to C. parvum infection. Adoptive transfer of unstimulated or antigen stimulated DCs into CD11c+ depleted CD11c-DTR-Tg mice resulted in an early decrease in parasite load at 4 days post infection. However, this response was transient since parasite load increased in mice engrafted with either unstimulated DCs or DCs stimulated with solubilized antigen by 6 days post infection. In contrast, in mice engrafted with DCs stimulated with live sporozoites, parasite load remained low during the entire period, suggesting the development of a more effective and sustained response. A corresponding increase in IFN-γ expression in T cells from spleen and mesenteric lymph nodes was also noted. Consistent with the in vivo engraftment study, DCs that are pulsed with live sporozoites in vitro and co-cultured with CD4+ and CD8+ T cells produced higher IFN-γ levels. Our study establishes the importance of DCs in susceptibility to infection by C. parvum and as important mediators of immune responses.