Ferreira Karen Spadari, Almeida Sandro Rogério
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Prof. Lineu Prestes, 580, Bloco 17, São Paulo, CEP: 05508-900, Brazil.
Immunol Lett. 2006 Mar 15;103(2):121-6. doi: 10.1016/j.imlet.2005.10.014. Epub 2005 Nov 8.
The development of the appropriate CD4 Th subset is important for disease resolution and several studies have shown that different outcomes of a disease can be obtained by influencing the commitment of precursors to either, Th1 or Th2 lineage. Dendritic cells (DCs) are able to initiate response in naïve T cells and they also participate in Th cell education. In the present study we demonstrated that purified gp43 lead to down-regulation of MHC-II and adhesion properties of immature DCs and in LPS-induced DCs maturation. It was also shown that purified gp43 from Paracoccidioides brasiliensis has the same inhibitory effect on IL-12 release. Mice infected with Paracoccidioides brasiliensis that received DCs plus gp43 plus LPS had a significant increase of the lung colony forming units when compared with control (not immunized) or those that received only DCs plus LPS. Thus, the granuloma morphology seen in immunized mice was different when compared with non-immunized controls. These data suggest that gp43 affects many functions of the host cells, indicating that these alterations might be used by Paracoccidioides brasiliensis to reduce the effectiveness of the immune response thus facilitating the establishment and fate of primary infection in susceptible host.
合适的CD4 Th亚群的发育对于疾病的消退很重要,并且多项研究表明,通过影响前体细胞向Th1或Th2谱系的分化,可以获得不同的疾病结局。树突状细胞(DC)能够启动幼稚T细胞的应答,并且它们也参与Th细胞的分化。在本研究中,我们证明纯化的gp43会导致未成熟DC的MHC-II和黏附特性下调,并影响LPS诱导的DC成熟。还表明,来自巴西副球孢子菌的纯化gp43对IL-12的释放具有相同的抑制作用。与对照(未免疫)或仅接受DC加LPS的小鼠相比,感染巴西副球孢子菌并接受DC加gp43加LPS的小鼠的肺集落形成单位显著增加。因此,与未免疫对照相比,免疫小鼠中观察到的肉芽肿形态有所不同。这些数据表明,gp43会影响宿主细胞的许多功能,这表明这些改变可能被巴西副球孢子菌利用来降低免疫反应的有效性,从而促进易感宿主中原发性感染的建立和发展。