Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Cell Rep. 2019 Sep 3;28(10):2659-2672.e6. doi: 10.1016/j.celrep.2019.08.004.
American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component β-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in vivo. This study represents a definitive characterization of the role of IL-32γ in the trained phenotype induced by β-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.
美国皮肤利什曼病是一种由利什曼原虫引起的虫媒寄生虫病。固有免疫细胞通过一种称为训练免疫的过程，对感染或卡介苗（BCG）接种产生长期的功能重编程，从而提供针对二次感染的非特异性保护。在这里，我们证明，用真菌细胞壁成分β-葡聚糖训练的单核细胞通过增强促炎细胞因子的产生，对巴西利什曼原虫引起的感染提供增强的保护。从机制上讲，这种增强的免疫反应依赖于白细胞介素 32（IL-32）的表达增加。使用人源化 IL-32 转基因小鼠进行的研究强调了这些发现在体内的临床意义。本研究明确了 IL-32γ在β-葡聚糖或 BCG 诱导的训练表型中的作用，其结果加深了我们对控制训练免疫和利什曼原虫感染控制的分子机制的理解。
