Abstract
Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a trematode zoonosis of interest in public health and livestock production. Like other helminths, F. hepatica modulates 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 that F. hepatica glycans 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 upon F. hepatica infection. 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 by F. hepatica and contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite.
Highlights
Fasciola hepatica is a worldwide-distributed parasitic flatworm that causes fasciolosis, a zoonotic disease that affects mainly livestock and causes significant economic losses worldwide [1]
Our results indicate that the Tn antigen expressed by F. hepatica can modulate the TLR2-induced maturation of human monocyte-derived dendritic cells (DCs) in a process mediated by hMGL by upregulating the production of IL-10 and TNFα
FhTE was highly recognized by hMGL and, to a lower extent, by Mannose receptor (MR), DC-SIGN, and DCIR, while it was not recognized by Dectin-1 or Langerin (Figure 1A)
Summary
Fasciola hepatica is a worldwide-distributed parasitic flatworm that causes fasciolosis, a zoonotic disease that affects mainly livestock and causes significant economic losses worldwide [1]. F. hepatica modulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines [2,3,4,5]. Immune Regulation of CD11c+ Cells by F. hepatica in their life cycles and pathology, since they can participate in immune escape [9] In this context, we have recently described that glycans structures produced by F. hepatica participate in the modulation of DC maturation and mediate the production of IL-10 and IL-4 during infection [10]
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