title: Fasciola hepaticaImmune Regulates CD11c+Cells by Interacting with the Macrophage Gal/GalNAc Lectin.
abstract: Fasciolosis, caused byFasciola hepaticaandFasciola gigantica, is a trematode zoonosis of interest in public health and livestock production. Like other helminths,F. hepaticamodulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines. In this work, we show thatF. hepaticaglycans increase Th2 immune responses by immunomodulating TLR-induced maturation and function of dendritic cells (DCs). This process was mediated by the macrophage Gal/GalNAc lectin (MGL) expressed on DCs, which recognizes the Tn antigen (GalNAc-Ser/Thr) on parasite components. More interestingly, we identified MGL-expressing CD11c+cells in infected animals and showed that these cells are recruited both to the peritoneum and the liver uponF. hepaticainfection. These cells express the regulatory cytokines IL-10, TNFα and TGFβ and a variety of regulatory markers. Furthermore, MGL+CD11c+cells expand parasite-specific Th2/regulatory cells and suppress Th1 polarization. The results presented here suggest a potential role of MGL in the immunomodulation of DCs induced byF. hepaticaand contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite.
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Paula
authors.initials: P
authors.lastname: Carasi
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Sofía
authors.initials: S
authors.lastname: Frigerio
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Valeria
authors.initials: V
authors.lastname: da Costa
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: van Vliet
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Verónica
authors.initials: V
authors.lastname: Noya
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Natalie
authors.initials: N
authors.lastname: Brossard
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: García-Vallejo
authors.affiliation: Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
authors.forename: Teresa
authors.initials: T
authors.lastname: Freire
keywords: C-type lectin receptors; dendritic cell; glycans; helminth; immune regulation; macrophage Gal/GalNAc lectin