title: Dendritic cells play a role in host susceptibility to Cryptosporidium parvum infection.
abstract: 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.
authors.affiliation: Atlanta VA Medical Center, Decatur, GA 30033, United States; Department of Pediatrics, Emory University, Atlanta, GA 30322, United States.
authors.forename: Brahmchetna
authors.initials: B
authors.lastname: Bedi
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, GA 30322, United States.
authors.forename: Nina N
authors.initials: NN
authors.lastname: McNair
authors.affiliation: Atlanta VA Medical Center, Decatur, GA 30033, United States; Department of Pediatrics, Emory University, Atlanta, GA 30322, United States. Electronic address: jmead@emory.edu.
authors.forename: Jan R
authors.initials: JR
authors.lastname: Mead
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004168:Diphtheria Toxoid / Q000276:immunology; D004198:Disease Susceptibility; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D018845:CD11 Antigens; D016207:Cytokines; D004168:Diphtheria Toxoid
keywords: CD11c-DTR-Tg; Cryptosporidium; Dendritic cells; Innate response