Abstract
BackgroundDendritic cells (DCs) are antigen-presenting cells that regulate T cell responses for many infectious diseases. The tissue-dwelling nematode Trichinella spiralis expresses paramyosin (TsPmy) not only as a structural protein but also as an immunomodulator to alleviate complement attack by binding to some host complement components. Whether TsPmy is involved in other immunomodulatory pathway and how TsPmy interacts with host DCs is still unknown.MethodsMouse bone marrow-derived DCs were incubated with recombinant TsPmy (rTsPmy) for activation. Maturation of DC was determined by the expression of surface markers CD40, CD80, CD86 and MHCII. The rTsPmy-pulsed DCs were co-incubated with T. spiralis-sensitized or naïve mouse CD4+ T cells to observe their activation on T cells and polarizing regulatory T cells using flow cytometry. Cytokines were measured by enzyme-linked immunosorbent assays (ELISA).Results TsPmy was able to activate mouse bone marrow-derived DCs to semi-mature status characterized by expressing surface CD40 and CD86, but not CD80 and MHCII. The semi-mature TsPmy-pulsed DCs were able to stimulate T. spiralis-sensitized CD4+ T cells to proliferate. Incubation of TsPmy-pulsed DCs with naïve CD4+ splenocytes polarized the latter to CD4+CD25+Foxp3+ regulatory T cells. However, mice immunized with rTsPmy only induce the CD4+CD25−Foxp3+ T cell population, associated with high level of IL-10, TGF-β and IL-17A.ConclusionsDuring T. spiralis infection, TsPmy plays an important role in modulating the host immune system by stimulating DCs to differentiate the CD4+ T cells to regulatory T cells, in addition to binding to components of the host complement cascade, as survival strategies to live in host.
Highlights
Dendritic cells (DCs) are antigen-presenting cells that regulate T cell responses for many infectious diseases
Semi-maturation of DCs after recombinant Trichinella spiralis expresses paramyosin (TsPmy) (rTsPmy) stimulation fluorescenceactivated cell sorting (FACS) data demonstrated that both rTsPmy and LPS significantly upregulated the expression of CD40 and CD86 on stimulated CD11c+ DCs compared to PBS control (rTsPmy vs PBS: CD40, tD(6) = 2.963, P = 0.044; CD86, tD(6) = 3.106, P = 0.037; LPS vs PBS, CD40, tD(6) = 3.547, P = 0.021; CD86, tD(6) = 4.213, P = 0.01) (Fig. 1)
Detection of cytokine production of DCs response to rTsPmy To further investigate if rTsPmy stimulates DCs to secrete Th1, Th2, Th17 and regulatory cytokines, IL-1β, IL-5, IL-6, IL-10, IL-17A, IL-12p70, IFN-γ, TNF-α and TGF-β were detected in culture supernatants of antigenstimulated DCs
Summary
Dendritic cells (DCs) are antigen-presenting cells that regulate T cell responses for many infectious diseases. The tissue-dwelling nematode Trichinella spiralis expresses paramyosin (TsPmy) as a structural protein and as an immunomodulator to alleviate complement attack by binding to some host complement components. Whether TsPmy is involved in other immunomodulatory pathway and how TsPmy interacts with host DCs is still unknown. Trichinellosis is a serious zoonotic parasitic disease caused by the infection of Trichinella spiralis through ingestion of meat contaminated with infective larvae. Subsequent studies have identified that TsPmy binds to host complement components C8, C9 and C1q that interferes with the forming of complement membrane attack complex and protects parasite from being attacked by the host innate immune system [12,13,14,15]. Except for interfering with host complement system, whether TsPmy is involved in other immunomodulatory function is unknown
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