Resposta imune a Candida albicans / Immune response to Candida albicans

Candida albicans causa infecções na pele, cavidade oral e esôfago, trato gastrointestinal, vagina e sistema vascular de humanos. As infecções ocorrem em hospedeiros imunocomprometidos ou pacientes debilitados. Acima de 90 por cento dos pacientes HIV+ sofrem de candidíase de mucosas ao menos uma vez no decorrer da doença. A severidade e cronicidade da candidíase oral em pacientes com AIDS são atribuídas, principalmente, à imunodeficiência induzida pelo HIV nos indivíduos afetados, a saber, perda de funções de célula T auxiliar e redução do número de linfócitos T CD4. Na colonização de mucosase infecções sistêmicas de camundongos por este fungo, células Th1 medeiam a proteção dependente de fagócitos, cujas citocinas mais importantes são IL-2, IFN-γ e IL-12, TNF-α. Ao contrario, produção de citocinas inibidoras tais como, IL-4 e IL-10 por células Th2 estão associadas à desativação de fagócitos e à progressão da doença. Possivelmente, o crescimento de formas filamentosas está melhor adaptado para evadir das células do sistema imune, enquanto a forma de levedura pode ser o modo de proliferação em tecidos infectados. Pela produção discriminativa de IL-12 em resposta a levedura e de IL-4 a hifa, as células dendríticas adquirem a capacidade para induzir a diferenciação de células TCD4 para o fenótipo Th1 ou Th2.

Candida albicans causes infections of the skin, oral cavity and esophagus, gastrointestinal tract, vaginaand vascular system. Most infections occur in immunocompromised hosts or debilitated patients. Morethan 90 percent of HIV positive patients suffer from mucosal candidiasis at least once in the course of thisdisease. The overall severity and chronicity of oral candidiasis in patients with AIDS are mainly attributedto the HIV-induced immune deficiency in the affected individuals, namely, the loss of T-helper cells andreduction in the number of CD4+ T lymphocytes. In mucosal colonization and systemic infections ofmice by this fungus, Th1 cells mediate phagocyte-dependent protection, whose most important cytokinesare IL-2, IFN-γ, TNF-α and IL-12. In contrast, production of inhibitory cytokines such as IL-4 and IL-10 by Th2 cells are associated with disactivation of phagocytes and disease progression. Possibly, thegrowth of filamentous forms is better adapted to evade the cells of the immune system, whereas theyeast form may be the mode of proliferation in infected tissues. By the discriminative production of IL-12 or IL-4 in response to the yeast or filamentous forms respectively, dendritic cells acquire the capacityof inducing the differentiation of CD4+ cells towards the Th1 or Th2 phenotypes.Keywords: Candida albicans. Immune response. Systemic infection.

Treatment of serum with supernatants from cultures of Candida albicans reduces its serum-dependent phagocytosis

Candida albicans is a potent activator of the complement system, and heat labile opsonins produced by activation of C3 (C3b and iC3b) enhance phagocytosis of C. albicans mediated by complement receptors. In this study we treated mouse serum with supernatants from cultures of a protease producer strain of C. albicans and evaluated the ability of this serum to enhance phagocytosis of C. albicans. Cell-free supernatants from cultures of C. albicans were concentrated 5 fold and added to mouse serum for 30 min at 37§C, before using this serum for opsonization of glutaraldehyde-fixed yeast cells. We observed that normal mouse serum increased about 3 fold the phagocytosis of C. albicans by mice peritoneal macrophages, whereas supernatant-treated serum did not increase phagocytosis. This effect of supernatants on serum was prevented by addition of pepstatin (5 µg/ ml; an inhibitor of C. albicans acid proteases) to the medium. Serum treated with supernatants from cultures of a protease-deficient mutant of C. albicans also increased about 3 fold phagocytosis of the yeast. These results suggest that a protease produced by C. albicans causes proteolysis of serum opsonins, thereby reducing the phagocytosis of the yeast.