Nosanchuk J D, Rosas A L, Casadevall A
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Immunol. 1998 Jun 15;160(12):6026-31.
Melanins are associated with virulence in several important human pathogens, but little is known about the immune response to this ubiquitous biologic compound. We hypothesized that melanin produced by the fungus Cryptococcus neoformans was immunogenic. C. neoformans melanin was purified from melanized fungal cells and was used to immunize C57BL/6, BALB/c, and T cell-deficient (nude) BALB/c mice. The Ab response was evaluated by ELISA, immunofluorescence, and agglutination. The results demonstrate that melanin can be immunogenic, and the humoral immune response is T cell independent. Furthermore, the experiments demonstrate 1) a sensitive ELISA for the measurement of Ab to melanin, 2) that mice mount an intense Ab response to fungal melanin that includes Abs of IgM and IgG isotypes, 3) that melanins from different sources have cross-reactive epitopes, and 4) melanin in the cell wall of melanized yeast cells reacts with Abs raised to L-dopa C. neoformans melanin. The biologic significance of Ab to melanin remains to be determined, but the development of Ab suggests that this amorphous insoluble polymer can stimulate the immune system. The serologic techniques described here may prove useful for the evaluation of Ab responses to melanin in a variety of diseases.
黑色素与几种重要的人类病原体的毒力相关，但对于这种普遍存在的生物化合物的免疫反应却知之甚少。我们推测新型隐球菌产生的黑色素具有免疫原性。从黑色素化的真菌细胞中纯化出新型隐球菌黑色素，并用于免疫C57BL/6、BALB/c和T细胞缺陷（裸）BALB/c小鼠。通过酶联免疫吸附测定（ELISA）、免疫荧光和凝集反应评估抗体反应。结果表明，黑色素可以具有免疫原性，并且体液免疫反应不依赖T细胞。此外，实验证明：1）一种用于测量抗黑色素抗体的灵敏ELISA方法；2）小鼠对真菌黑色素产生强烈的抗体反应，包括IgM和IgG同种型的抗体；3）不同来源的黑色素具有交叉反应性表位；4）黑色素化酵母细胞细胞壁中的黑色素与针对左旋多巴产生的新型隐球菌黑色素的抗体发生反应。抗黑色素抗体的生物学意义尚待确定，但抗体的产生表明这种无定形不溶性聚合物可以刺激免疫系统。本文所述的血清学技术可能被证明对评估多种疾病中抗黑色素的抗体反应有用。
