Characterization of dendritic cells and follicular dendritic cells in the hepatic lymph nodes and liver of sheep experimentally infected with Fasciola hepatica

Abstract

Fasciola hepatica has been shown to have a high capacity for immunomodulation of the host response, making the development of protective vaccines extremely difficult. One of these immunomodulation mechanisms is the impairment of dendritic cells (DC) maturation and, therefore, suppression of antigenic presentation. The aim of this study was to evaluate the pathological changes as well as the characterization of two antigen presenting cells, DC (CD1b, CD83 and MHC-II positive) and follicular dendritic cells (FDC) (CNA.42, S100 and CD83 positive) by immunohistochemistry in the hepatic lymph nodes (HLN) and livers of sheep during the early stages of infection with F. hepatica [9 and 18 days post-infection (dpi)], compared with an uninfected group (UC) as a control. The results revealed a marked hyperplasia of HLN germinal centres at 9 and, in particular, 18 dpi, with respect to the UC group, with coincidental increased expression of CNA.42 in FDC of lymphoid follicles and CD1b in the DC of paracortical areas at 18 dpi. However, the expression of MHC-II and CD83 decreased at 9 and, particularly, at 18 dpi in HLN compared with that in the UC group. Since both markers are related to active presentation of antigens by DC and FDC, the results of the present study suggest that, despite the marked hyperplasia of HLN and increase in DC and FDC numbers during early stages of infection, the DC and FDC antigenic presentation capacity, as suggested by the expression of the markers MHC-II and CD83, is suppressed by the parasite. This suppression was not observed in the liver, probably because of the low number of DC. This is the first study of the immunophenotype of DCs and FDC in sheep infected with F. hepatica.

Transcriptomic Analysis of Ovine Hepatic Lymph Node Following Fasciola hepatica Infection – Inhibition of NK Cell and IgE-Mediated Signaling

“…Furthermore, Falcoń et al (80) found that DC stimulated with F. hepatica excretory-secretory products (ESP) primed CD4+ cells towards a T h 2/regulatory response, with increased production of IL-4, IL-5, IL-10 and TGF-b, and reduced IFN-g. Some of these changes have been observed in sheep, where infection with F. hepatica produced hyperplasia of the hepatic lymph nodes with increased numbers of DC at 18 dpi, but a significant decrease in the expression of their antigen presentation markers (CD83 and MHC-II) (85). Our results indicate an increased expression of both the CD83 and CD40 genes, which could indicate a difference between acute and chronic infections.…”

Fasciola hepatica primoinfections and reinfections in sheep drive distinct Th1/Th2/Treg immune responses in liver and hepatic lymph node at early and late stages

“…This makes chronicity one of the consequences of the regulated milieu induced by the parasite, and the main obstacle in producing an effective vaccine [16,17]. The capacity of F. hepatica to downregulate the Th1 proinflammatory immune response and upregulate the Th2 anti-inflammatory immune response beginning at early stages of infection in sheep has been previously described [18][19][20][21][22]. This scenario implies the downregulation of IFN-γ expression and the upregulation of IL-4 expression, leading to the suppression of the Th1 pro-inflammatory immune response and promoting a Th2 non-protective immune response.…”

Fasciolosis: pathogenesis, host-parasite interactions, and implication in vaccine development

“…In addition, F. hepatica cathepsin L1 (FhCL1), glutathione S-transferase (FhGST), and Kunitz-type molecule participate in the modulation of DCs, leading to the suppression of the adaptive immune responses, Th1, and/or Th17 ( 40 , 97 ). F. hepatica -infected sheep showed increased numbers of DCs in the hepatic lymph nodes but reduced expression of MHC class II and CD83, suggesting suppression of the antigen-presentation process in lymphocytes both in the early and late stages of infection ( 125 ).…”