Navegando por Palavras-chave "flagellin"

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    CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8 alpha(+) and CD8 alpha(-) Conventional Dendritic Cell Subsets
    (Frontiers Media Sa, 2017) Antonialli, Renan; Sulczewski, Fernando Bandeira; da Silva Amorim, Kelly Nazare; Almeida, Bianca da Silva; Ferreira, Natalia Soares; Yamamoto, Marcio Massao; Soares, Irene Silva; de Souza Ferreira, Luis Carlos; Rosa, Daniela Santoro [UNIFESP]; Boscardin, Silvia Beatriz
    Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets through the use of hybrid monoclonal antibodies (mAbs) to DC surface receptors fused to antigens of interest opened new perspectives for the induction of robust immune responses. Normally, the hybrid mAbs are administered with adjuvants that induce DC maturation. In this work, we targeted an antigen to the CD8 alpha(+) or the CD8 alpha(-) DC subsets in the presence of CpG oligodeoxinucleotides (ODN) or bacterial flagellin, using hybrid alpha DEC205 or alpha DCIR2 mAbs, respectively. We also accessed the role of toll-like receptors (TLRs) 5 and 9 signaling in the induction of specific humoral and cellular immune responses. Wild-type and TLR5 or TLR9 knockout mice were immunized with two doses of the hybrid alpha DEC205 or alpha DCIR2 mAbs, as well as with an isotype control, together with CpG ODN 1826 or flagellin. A chimeric antigen containing the Plasmodium vivax 19 kDa portion of the merozoite surface protein (MSP1(19)) linked to the Pan-allelic DR epitope was fused to each mAb. Specific CD4(+) T cell proliferation, cytokine, and antibody production were analyzed. We found that CpG ODN 1826 or flagellin were able to induce CD4(+) T cell proliferation, CD4(+) T cells producing pro-inflammatory cytokines, and specific antibodies when the antigen was targeted to the CD8 alpha(+) DC subset. On the other hand, antigen targeting to CD8 alpha(-) DC subset promoted specific antibody responses and proliferation, but no detectable pro-inflammatory CD4(+) T cell responses. Also, specific antibody responses after antigen targeting to CD8 alpha(+) or CD8 alpha(-) DCs were reduced in the absence of TLR9 or TLR5 signaling, while CD4(+) T cell proliferation was mainly affected after antigen targeting to CD8 alpha(+) DCs and in the absence of TLR9 signaling. These results extend our understanding of the modulation of specific immune responses induced by antigen targeting to DCs in the presence of different adjuvants. Such knowledge may be useful for the optimization of DC-based vaccines.
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    Cytotoxic T cell adjuvant effects of three Salmonella enterica flagellins
    (Sociedade Brasileira de Microbiologia, 2008-03-01) Braga, Catarina J.m.; Massis, Liliana M.; Alencar, Bruna C.g. [UNIFESP]; Rodrigues, Mauricio Martins [UNIFESP]; Sbrogio-Almeida, M.e.; Ferreira, Luís Carlos de Souza; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Instituto Butantan Divisião de Produção e Desenvolvimento Tecnológico
    Bacterial flagellins are important virulence-associated factors and strong inducers of inflammatory responses in mammalian hosts. Flagellins have also been investigated as potential vaccine adjuvants, either for induction of humoral or cellular immune responses, to different target antigens. In this study we investigated the adjuvant properties of three Salmonella enterica flagellins types (FliCd, FliCi and FljB) to an ovalbumin-derived CD8+ T cell-restricted epitope (OVA257264). Although mice immunized with the three tested flagellins elicited antigen-specific activated CD8+ T cells, only animals immunized with FliCi and FliCd flagellins admixed with ovalbumin mounted specific in vivo cytotoxic responses to peptide-pulsed target cells. The present results indicate that Salmonella flagellins are endowed with type-specific adjuvant effects toward murine CD8+ T cells, a feature that may impact their use as adjuvants for prophylatic or therapeutic vaccines.
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    Emerging concepts about NAIP/NLIRC4 inflammasomes
    (Frontiers Research Foundation, 2014-07-02) Lage, Silvia Lucena [UNIFESP]; Longo, Carla [UNIFESP]; Branco, Laura Migliari [UNIFESP]; Costa, Thais Boccia da [UNIFESP]; Buzzo, Carina de Lima [UNIFESP]; Bortoluci, Karina Ramalho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically associate with NLRC4 to form an inflammasome complex able to recruit and activate pro-caspase-1. NAIP5 and NAIP6 sense flagellin, component of flagella from motile bacteria, whereas NAIP1 and NAIP2 detect needle and rod components from bacterial type III secretion systems, respectively. Active caspase-1 mediates the maturation and secretion of the pro-inflammatory cytokines, 11,113 and 11,18, and is responsible for the induction of pyroptosis, a pro-inflammatory form of cell death. in addition to these well-known effector mechanisms, novel roles have been described for NAIP/NLRC4 inflammasomes, such as phagosomal maturation, activation of inducible nitric oxide synthase, regulation of autophagy, secretion of inflammatory mediators, antibody production, activation of T cells, among others. These effector mechanisms mediated by NAIP/NLRC4 inflammasomes have been extensively studied in the context of resistance of infections and the potential of their agonists has been exploited in therapeutic strategies to non-infectious pathologies, such as tumor protection. Thus, this review will discuss current knowledge about the activation of NAIP/NLRC4 inflammasomes and their effector mechanisms.
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    TLR5-dependent immunogenicity of a recombinant fusion protein containing an immunodominant epitope of malarial circumsporozoite protein and the FliC flagellin of Salmonella Typhimurium
    (Fundaco Oswaldo Cruz, 2011-08-01) Camacho, Ariane Guglielmi Ariza [UNIFESP]; Teixeira, Lais Helena [UNIFESP]; Bargieri, Daniel Youssef [UNIFESP]; Boscardin, Silvia Beatriz; Soares, Irene da Silva; Nussenzweig, Ruth Sonntag; Nussenzweig, Victor; Rodrigues, Mauricio Martins [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); NYU
    Recently, we described the improved immunogenicity of new malaria vaccine candidates based on the expression of fusion proteins containing immunodominant epitopes of merozoites and Salmonella enterica serovar Typhimurium flagellin (FliC) protein as an innate immune agonist. Here, we tested whether a similar strategy, based on an immunodominant B-cell epitope from malaria sporozoites, could also generate immunogenic fusion polypeptides. A recombinant His6-tagged FliC protein containing the C-terminal repeat regions of the VK210 variant of Plasmodium vivax circumsporozoite (CS) protein was constructed. This recombinant protein was successfully expressed in Escherichia coli as soluble protein and was purified by affinity to Ni-agarose beads followed by ion exchange chromatography. A monoclonal antibody specific for the CS protein of P. vivax sporozoites (VK210) was able to recognise the purified protein. C57BL/6 mice subcutaneously immunised with the recombinant fusion protein in the absence of any conventional adjuvant developed protein-specific systemic antibody responses. However, in mice genetically deficient in expression of TLR5, this immune response was extremely low. These results extend our previous observations concerning the immunogenicity of these recombinant fusion proteins and provide evidence that the main mechanism responsible for this immune activation involves interactions with TLR5, which has not previously been demonstrated for any recombinant FliC fusion protein.