Abstract
Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica (Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-γ secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-γ secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies.
Highlights
In ruminants[15,16,17]
Dendritic cells (DCs) from mice infected with F. hepatica have a semi-mature phenotype that is characterized by low MHC class II (MHC II) and CD40 expression and high secretion of the immunoregulatory cytokine IL-1025
In this work we show that a mucin-derived peptide from F. hepatica can enhance LPS-triggered maturation of DCs, and can stimulate F. hepatica-specific T cell responses when associated to a Th1-driven stimulus such as LPS
Summary
In ruminants[15,16,17]. Interestingly, it has been proposed that induction of a robust Th1 response could protect the host from the infection[15,18] and from bystander co-infections by down-regulating Th2 regulatory immunity[19]. DCs from mice infected with F. hepatica have a semi-mature phenotype that is characterized by low MHC II and CD40 expression and high secretion of the immunoregulatory cytokine IL-1025. Given their remarkable capacity to present antigens to T cells, antigen-loaded DCs have been proposed as vaccines to prevent a spectrum of infectious diseases[26,27,28,29,30]. DCs pulsed with certain helminths, have been shown to protect against infection, in vaccination regimens[26] Supporting this concept, bone marrow derived-DCs (BMDCs) loaded with F. hepatica antigens in the presence of LPS protected mice against parasite infection[26]. This work highlights the immunostimulatory role of a mucin-derived peptide from F. hepatica, with potential implications in vaccination strategies against this flatworm
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