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.
Highlights
Fasciolosis, caused by F. hepatica, results in major economic losses to the agricultural sector [1]
It has been determined that different antigenic preparations of this parasite, such as total extract, F. hepatica tegumental antigen (FhTeg) and excretory-secretory products (ESPs), decrease the activation state of dendritic cells (DC) in mice [11, 12, 18, 19], and F. gigantica ESPs induce the modulation of buffalo DC [20]
The CNA.42 antibody was expressed mainly by follicular dendritic cells (FDC) located in the light zones of the germinal centres of lymphoid follicles, an expression pattern that was reported for human [41] and sheep [13] lymph nodes using the same antibody
Summary
Fasciolosis, caused by F. hepatica, results in major economic losses to the agricultural sector [1]. It has been reported that F. hepatica is able to downregulate the Th1 immune response and upregulate the Th2 response at early stages of infection in sheep [15] and mice [16], as well as in chronic stages in cattle [17]. This imbalance towards a Th2 immune profile is mediated through regulatory cytokines and cells, such as DC, that modulate and/or suppress inflammatory responses. The effect of F. hepatica infection on FDC has not been evaluated
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