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      The Immune Response to Trypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development

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          Abstract

          In the past ten years, studies have shown the recognition of Trypanosoma cruzi-associated molecular patterns by members of the Toll-like receptor (TLR) family and demonstrated the crucial participation of different TLRs during the experimental infection with this parasite. In the present review, we will focus on the role of TLR-activated pathways in the modulation of both innate and acquired immune responses to T. cruzi infection, as well as discuss the state of the art of vaccine research and development against the causative agent of Chagas disease (or American trypanosomiasis).

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          Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

          J Paavonen, P Naud, J. Salmerón … (2009)
          The Lancet, 374(9686), 301-314
          Article 0 comments Cited 449 times – based on 0 reviews     Review now
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            The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults.

            B. Lemaitre, E. Nicolás, L Michaut … (1996)
            The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.
            Article 0 comments Cited 369 times – based on 0 reviews     Review now
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              The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4.

              Veronica Mata-Haro, Caglar Cekic, Michael Martin … (2007)
              The inflammatory toxicity of lipopolysaccharide (LPS), a component of bacterial cell walls, is driven by the adaptor proteins myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta (TRIF), which together mediate signaling by the endotoxin receptor Toll-like receptor 4 (TLR4). Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with useful immunostimulatory properties, which is nearing regulatory approval for use as a human vaccine adjuvant. We report here that, in mice, the low toxicity of MPLA's adjuvant function is associated with a bias toward TRIF signaling, which we suggest is likely caused by the active suppression, rather than passive loss, of proinflammatory activity of this LPS derivative. This finding may have important implications for the development of future vaccine adjuvants.
              Article 0 comments Cited 246 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Parasitol Res
                Journal ID (publisher-id): JPR
                Title: Journal of Parasitology Research
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-0023
                ISSN (Electronic): 2090-0031
                Publication date (Print): 2012
                Publication date (Electronic): 16 February 2012
                Volume: 2012
                Electronic Location Identifier: 507874
                Affiliations
                1Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo (UNIFESP), 04044-010 São Paulo, SP, Brazil
                2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), 21941-902 Rio de Janeiro, RJ, Brazil
                3Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), CCS, Avenida Carlos Chagas Filho, 373 Bloco D, sala 35, Cidade Universitária, 21941-902 Rio de Janeiro, RJ, Brazil
                Author notes

                Academic Editor: Marcela F. Lopes

                Article
                DOI: 10.1155/2012/507874
                PMC ID: 3306967
                PubMed ID: 22496959
                SO-VID: 9612b07a-4aa3-4af1-a2d1-5b50db7c2262
                Copyright © Copyright © 2012 Mauricio M. Rodrigues et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 1 September 2011
                Date accepted : 31 October 2011
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Parasitology
                Data availability:
                ScienceOpen disciplines: Parasitology

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