title: Interaction of Cryptosporidium parvum with mouse dendritic cells leads to their activation and parasite transportation to mesenteric lymph nodes.
abstract: Dendritic cells (DCs) are the antigen-presenting cells capable of activating naïve T cells. Although CD4+ T cells are crucial for Cryptosporidium parvum clearance, little is known about the role of DCs in the immune response to this parasite. In this study, the interaction between mouse DCs and C. parvum was investigated both in vitro and in vivo. For in vitro experiments, mouse bone marrow-derived dendritic cells (BMDCs) derived from wild-type C57B1/6 or MyD88-/- or C3H/HeJ mice and DC cell line DC2.4 were pulsed with C. parvum. Active invasion of parasites was demonstrated by parasite colocalization with host cell membranes and actin-plaque formation at the site of attachment. DC activation induced by the parasite invasion was demonstrated by upregulation of costimulatory molecules CD40, CD80, and CD86, as well as inflammatory cytokines IL-12, TNF-α, and IL-6. BMDCs derived from MyD88-/- and C3H/HeJ mice failed to produce IL-12 in response to C. parvum, suggesting the importance of TLR-dependent signaling pathway specially presence of a functional TLR4 pathway, for C. parvum-induced cytokine production. In vivo experiments showed that both parasite antigens and live parasites were transported to mice mesenteric lymph nodes. All together, these data suggest that DCs play a key role in host immune responses to C. parvum and pathogenesis of the disease.
authors.affiliation: Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Perez-Cordon
authors.forename: Guilin
authors.initials: G
authors.lastname: Yang
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.forename: Weijia
authors.initials: W
authors.lastname: Nie
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Lianfa
authors.initials: L
authors.lastname: Shi
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000469:parasitology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000469:parasitology; D003457:Cryptosporidiosis / Q000276:immunology* / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015850:Interleukin-6; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: Cryptosporidium parvum; dendritic cell; mesenteric lymph node
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