Melanin is a Sporothrix virulence factor that can inhibit the innate immune functions of macrophages such as phagocytosis and killing. However, no data on melanin's influence on antigen presentation by macrophages are available. In this study, we used conidia, yeasts, and melanin ghosts (MGs) from a black Sporothrix globosa strain (MEL+) and its ultraviolet-induced albino mutant (MEL-), to study the influence of melanin on expression of molecules involved in antigen presentation by mouse macrophages (MHC class II, CD80, CD86), as well as on levels of transcription factors regulating their expression (CIITA and promoters I, III, and IV). A murine infection model was used to assess the virulence of both strains and differences in expression of MHC class II and CD80/86 in vivo. MHC class II, CD86 CIITA, and PIV expressions were lower in macrophages infected with MEL+ than in macrophages infected with MEL- conidia, while CD80 expression was similar. No statistical difference in gene expression was observed between macrophages infected by MEL+ and MEL- yeasts. Infection by MGs alone had no clear effect on expression of antigen presentation-associated molecules. Mice infected with MEL+ S. globosa had significantly higher fungal burdens in the lung, liver, spleen, kidney, and testicle compared with mice infected with MEL- S. globosa 21 days post-infection. MHC class II expression changes in the animal study were similar to those observed in the in vitro experiment. Our results indicate that S. globosa melanin can inhibit expression of antigen presentation-associated molecules during both the early and late stages of infection, representing a new mechanism to evade host immunity and to enhance dissemination. Further investigations of melanin's impact on adaptive immunity will be helpful in understanding this fungal virulence factor.

中文翻译：

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球形孢子丝黑色素抑制巨噬细胞抗原呈递并增强深部器官传播

黑色素是一种孢子丝菌毒力因子，可以抑制巨噬细胞的吞噬、杀伤等先天免疫功能。然而，没有关于黑色素对巨噬细胞抗原呈递影响的数据。在本研究中，我们使用来自黑色球形孢子丝菌 (MEL+) 及其紫外线诱导的白化突变体 (MEL-) 的分生孢子、酵母和黑色素影 (MGs)，研究黑色素对抗原相关分子表达的影响由小鼠巨噬细胞（MHC II 类、CD80、CD86）呈递，以及调节其表达的转录因子水平（CIITA 和启动子 I、III 和 IV）。鼠感染模型用于评估两种菌株的毒力以及体内 MHC II 类和 CD80/86 的表达差异。MHC II 类，CD86 CIITA，感染 MEL+ 的巨噬细胞和 PIV 表达低于感染 MEL- 分生孢子的巨噬细胞，而 CD80 表达相似。在被 MEL+ 和 MEL- 酵母感染的巨噬细胞之间没有观察到基因表达的统计学差异。MG 单独感染对抗原呈递相关分子的表达没有明显影响。感染 MEL+ S. globosa 的小鼠在感染后 21 天与感染 MEL- S. globosa 的小鼠相比，其肺、肝、脾、肾和睾丸中的真菌负荷显着增加。动物研究中的 MHC II 类表达变化与体外实验中观察到的相似。我们的结果表明，S. globosa 黑色素可以在感染的早期和晚期抑制抗原呈递相关分子的表达，代表一种逃避宿主免疫和加强传播的新机制。进一步研究黑色素对适应性免疫的影响将有助于了解这种真菌毒力因子。