RESUMO
Hyperthermophile microorganisms have been discovered worldwide, and several studies regarding biodiversity and the potential biotechnological applications have been reported. In this work, we describe for the first time the diversity of hyperthermophile communities in the Calientes Geothermal Field (CGF) located 4400 m above sea level in Tacna Region, Perú. Three hot springs were monitored and showed a temperature around 84 to 88 °C, for the microbiome analyzed was taken by sampling of sediment and water (pH 7.3-7.6). The hyperthermophile diversity was determined by PCR, DGGE, and DNA sequencing. The sediments analyzed showed a greater diversity than water samples. Sediments showed a more abundant population of bacteria than archaea, with the presence of at least 9 and 5 phylotypes, respectively. Most interestingly, in some taxa of bacteria (Bacillus) and archaea (Haloarcula and Halalkalicoccus), any of operational taxonomic units (OTUs) have not been observed before in hyperthermophile environments. Our results provide insight in the hyperthermophile diversity and reveal the possibility to develop new biotechnological applications based on the kind of environments.
Assuntos
Halobacteriaceae , Fontes Termais , Microbiota , Peru , Archaea/genética , Bactérias/genética , Halobacteriaceae/genética , Fontes Termais/microbiologia , Biodiversidade , Água , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B-cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls and patients with SLE were treated with dexamethasone and rosiglitazone to induce tolDCs. Autologous apoptotic lymphocytes generated by UV irradiation were given to tolDCs as a source of self-antigens. Lipopolysaccharide (LPS) was used as a maturation stimulus to induce the expression of co-stimulatory molecules and secretion of cytokines. TolDCs generated from patients with SLE showed a reduced expression of co-stimulatory molecules after LPS stimulation compared with mature DCs. The same phenomenon was observed in tolDCs treated with ApoCells and LPS. In addition, ApoCell-loaded tolDCs stimulated with LPS secreted lower levels of interleukin-6 (IL-6) and IL-12p70 than mature DCs without differences in IL-10 secretion. The functionality of tolDCs was assessed by their capacity to prime allogeneic T cells. TolDCs displayed suppressor properties as demonstrated by a significantly reduced capacity to induce allogeneic T-cell proliferation and activation. ApoCell-loaded tolDCs generated from SLE monocytes have a stable immature/tolerogenic phenotype that can modulate CD4+ T-cell activation. These properties make them suitable for an antigen-specific immunotherapy for SLE.
Assuntos
Células Dendríticas/transplante , Terapia de Imunossupressão/métodos , Lúpus Eritematoso Sistêmico/terapia , Monócitos/transplante , Doadores de Tecidos , Adulto , Idoso , Autoenxertos , Células Dendríticas/imunologia , Feminino , Humanos , Interleucina-10/imunologia , Interleucina-12/imunologia , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Raios UltravioletaRESUMO
Dendritic cells (DCs) play a key role in the activation of the immune response against pathogens, as well as in the modulation of peripheral tolerance to self-antigens (Ags). Furthermore, an imbalance in the activating/inhibitory receptors expressed on the surface of DCs has been linked to increased susceptibility to develop autoimmune diseases underscoring their immunogenicity potential. It has been described that modulation of activating or inhibitory molecules expressed by DCs, such as CD86, TLRs, PDL-1 and FcγRs, can define the immunogenic phenotype. On the other hand, T cell tolerance can be achieved by tolerogenic DCs, which have the capacity of blocking undesired autoimmune responses in several experimental models, mainly by inducing T cell anergy, expansion of regulatory T cells and limiting B cell responses. Due to the lack of specific therapies to treat autoimmune disorders and the tolerogenic capacity of DCs shown in experimental autoimmune disease models, autologous tolDCs are a potential therapeutic strategy for fine-tuning the immune system and reestablishing tolerance in human autoimmune diseases. New advances in the role of DCs in systemic lupus erythematosus (SLE) pathogenesis and the identification of pathogenic self-Ags may favor the development of novel tolDC based therapies with a major clinical impact. In this review, we discuss recent data relative to the role of DCs in systemic autoimmune pathogenesis and their use as a therapy to restore tolerance.
Assuntos
Doenças Autoimunes/imunologia , Células Dendríticas/imunologia , Animais , Autoantígenos/imunologia , Linfócitos B/imunologia , Humanos , Tolerância Imunológica/imunologia , Receptores Toll-Like/imunologiaRESUMO
Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders.
Assuntos
Doenças Autoimunes/patologia , Células Dendríticas/imunologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/metabolismo , Linfócitos B/imunologia , Colecalciferol/uso terapêutico , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Tolerância Imunológica , Nitrilas/uso terapêutico , Sulfonas/uso terapêutico , Linfócitos T/imunologiaRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by the over production of auto-antibodies against nuclear components. Thus, SLE patients have increased morbidity and, mortality compared to healthy individuals. Available therapies are not curative and are associated with unwanted adverse effects. During the last few years, important advances in immunology research have provided rheumatologists with new tools for designing novel therapies for treating autoimmunity. However, the complex nature of SLE has played a conflicting role, hindering breakthroughs in therapeutic development. Nonetheless, new advances about SLE pathogenesis could open a fruitful line of research. Dendritic cells (DCs) have been established as essential players in the mechanisms underlying SLE, making them attractive therapeutic targets for fine-tuning the immune system. In this review, we discuss the recent advances made in revealing the mechanisms of SLE pathogenesis, with a focus on the use of DCs as a target for therapy development.