Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro.

Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii. The main clinical manifestations occur in the skin, however the number of systemic and visceral cases has increased, especially in immunocompromised patients. Dendritic cells (DCs) are highly capable to recognize the fungus associated data and translate it into differential T cells responses both in vivo and in vitro. Although, the mechanisms involved in the interaction between DCs and S. schenckii are not fully elucidated. The present study investigated the phenotypic and functional changes in bone marrow dendritic cells (BMDCs) stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and its ability to trigger a cellular immune response in vitro. Our results demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher dose, were able to activate BMDCs and made them capable of triggering T cell responses in vitro. Whereas the yeast group promoted more pronounced IFN-γ production rather than IL-17, the Exo100 group generated similar production of both cytokines. The exoantigen stimulus suggests a capability to deviate the immune response from an effector Th1 to an inflammatory Th17 response. Interestingly, only the Exo100 group promoted the production of IL-6 and a significant increase of TGF-ß, in addition to IL-23 production. Interestingly, only Exo100 group was capable to promote the production of IL-6 and a significant increase on TGF-ß, in addition with IL-23 detection. Our results demonstrated the plasticity of DCs in translating the data associated with the fungus S. schenckii and ExoAg into differential T cell responses in vitro. The possibility of using ex vivo-generated DCs as vaccinal and therapeutic tools for sporotrichosis is a challenge for the future.

Role of Yersinia pseudotuberculosis outer proteins (Yops) in murine humoral immune response.

The infection of mice with the wild-type (WT) strain of Y. pseudotuberculosis did not induce polyclonal activation of B lymphocytes. Suppression in the production of certain isotypes of Ig was observed, provoked mainly by YopH, YopJ and YpkA. The WT strain induced a progressive increase in the serum-specific IgG, which peaked after 4 weeks after infection, IgM being produced only after 1 week. Autoantibodies against phosphorylcholine, myelin, thyroglobulin and cardiolipin could be detected in the serum of mice infected with the WT strain. The infection of mice provoked suppression in the production of immunoglobulins by splenic B cells and that YopH, YopJ and YpkA must be involved here.

Papel das Yops secretadas por Yersinia sobre a resposta imune do hospedeiro / Role of Yops secreted by Yersinia in the host immune response

O gênero Yersinia compreende três espécies patogênicas para humanos: Y. pestis, Y. enterocolitica e Y. pseudotuberculosis. A patogenicidade de Yersinia está ligada à presença do plasmideo de 70-kb (pYV) que é comum às três espécies e codifica um sistema de secreção do tipo III e um conjunto de proteínas de virulência, incluindo aquelas conhecidas como Yops (Yersinia outer proteins), que são exportadas por este sistema quando as células do hospedeiro são infectadas pela bactéria. Duas Yops translocadoras (YopB e YopD) se inserem na membrana plasmática e funcionam no transporte de seis efetoras (YopO, YopH, YopM, YopJ e YopT) para o citosol da célula do hospedeiro. As Yops efetoras funcionam interferindo em múltiplas vias de sinalização da célula infectada. Como consequência, a resposta imune inata e adaptativa do hospedeiro fica afetada. Este trabalho enfoca o papel das Yops na modulação da resposta imune do hospedeiro