IL-12 and TNF-alpha production by dendritic cells stimulated with Schistosoma mansoni schistosomula tegument is TLR4- and MyD88-dependent.

Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, A. Belo Horizonte, Minas Gerais, Brazil.
Immunology letters (Impact Factor: 2.91). 07/2009; 125(1):72-7. DOI: 10.1016/j.imlet.2009.06.004
Source: PubMed

ABSTRACT Schistosoma mansoni schistosomula are the most susceptible parasite life stage to host immune system attack. Complex host-parasite interactions take place on Schistosoma tegument, which is a unique double membrane structure involved in nutrition and immune evasion. Herein, we have demonstrated that schistosomula tegument (Smteg) activates Dendritic cells to produce IL-12p40, TNF-alpha and also to up-regulate the co-stimulatory molecules CD40 and CD86. Moreover, using DCs derived from MyD88-, TLR2-, TLR4- and TLR9-deficient mice we have shown that the ability of Smteg to activate DCs to produce IL-12 and TNF-alpha involves TLR4/Smteg interaction and MyD88 signaling pathway. Finally, our findings lead us to conclude that TLR4 is a key receptor involved in Smteg induction of pro-inflammatory cytokines.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Schistosoma mansoni tegument interaction with the immune system plays a key role in disease establishment or elimination. We have recently demonstrated that S. mansoni schistosomula tegument (Smteg) is able to activate innate immune response and to induce protective immunity in a vaccine formulation with Freunds adjuvant. In this work, we evaluated the ability of Smteg to elicit protection in the absence of adjuvant. Smteg mice immunization resulted in significant antibody production, increased percentage of CD4+IFN-g+ and CD4+IL-10+ cells in spleen and increased production of IFN-g and IL-10 by spleen cells, but failed to reduce parasite burden, female fecundity and morbidity. We also demonstrated that BMDC stimulation with Smteg resulted in significant IL-10 production. Our results demonstrate that Smteg has immune modulatory proprieties.
    Acta tropica 07/2012; 124(2):140-6. · 2.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of a vaccine against schistosomiasis and also the availability of a more sensitive diagnosis test are important tools to help chemotherapy in controlling disease transmission. Bioinformatics tools, together with the access to parasite genome, published recently, should help generate new knowledge on parasite biology and search for new vaccines or therapeutic targets and antigens to be used in the disease diagnosis. Parasite surface proteins, especially those expressed in schistosomula tegument, represent interesting targets to be used in vaccine formulations and in the diagnosis of early infections, since the tegument represents the interface between host and parasite and its molecules are responsible for essential functions to parasite survival. In this paper we will present the advances in the development of vaccines and diagnosis tests achieved with the use of the information from schistosome genome focused on parasite tegument as a source for antigens.
    Journal of Parasitology Research 01/2012; 2012:541268.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated. Water-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ∼190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ∼130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28-23 kDa region suggested that they are composed of actin. Immunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a challenging S. mansoni infection by mechanism(s) that still has to be elucidated.
    PLoS Neglected Tropical Diseases 06/2013; 7(6):e2254. · 4.57 Impact Factor