Department of Pharmaceutical Sciences, Federal University of São Paulo campus Diadema, Diadema, São Paulo, Brazil.
Department of Medicine/Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil.
J Leukoc Biol. 2020 Dec;108(6):1803-1814. doi: 10.1002/JLB.3MA0220-464RR. Epub 2020 Apr 30.
B-1 cells are a B-lymphocyte subtype whose roles in immunity are not completely defined. These cells can produce cytokines (mainly IL-10) and natural and specific antibodies. Currently, extracellular vesicles (EVs) released by immune cells have emerged as new important entities in cell-cell communication. Immune cells release EVs that can activate and/or modulate other immune cells. Here, we characterized the EVs released by peritoneal B-1 cells infected or not with Leishmania (Leishmania) amazonensis. This Leishmania species causes cutaneous leishmaniasis and can infect macrophages and B-1 cells. Our results showed that peritoneal B-1 cells spontaneously release EVs, but the parasite stimulated an increase in EVs production by peritoneal B-1 cells. The treatment of BALB/c and C57BL/6 bone marrow-derived macrophages (BMDM) with EVs from infected peritoneal B-1 cells led to differential expression of iNOS, IL-6, IL-10, and TNF-α. Additionally, BALB/c mice previous treated with EVs released by peritoneal B-1 cells showed a significant lower lesion size and parasite burden. Thus, this study demonstrated that peritoneal B-1 cells could release EVs that can alter the functions of macrophages in vitro and in vivo these EVs altered the course of L. amazonensis infection. These findings represent the first evidence that EVs from peritoneal B-1 cells can act as a new mechanism of cellular communication between macrophages and B-1 cells, contributing to immunity against experimental leishmaniasis.
B-1 细胞是 B 淋巴细胞亚型，其在免疫中的作用尚未完全确定。这些细胞可以产生细胞因子（主要是 IL-10）和天然及特异性抗体。目前，免疫细胞释放的细胞外囊泡（EVs）已成为细胞间通讯的新的重要实体。免疫细胞释放的 EVs 可以激活和/或调节其他免疫细胞。在这里，我们对感染或未感染 Leishmania（Leishmania）amazonensis 的腹腔 B-1 细胞释放的 EVs 进行了表征。这种 Leishmania 物种会引起皮肤利什曼病，并且可以感染巨噬细胞和 B-1 细胞。我们的结果表明，腹腔 B-1 细胞会自发释放 EVs，但寄生虫刺激腹腔 B-1 细胞产生更多的 EVs。用感染的腹腔 B-1 细胞释放的 EVs 处理 BALB/c 和 C57BL/6 骨髓来源的巨噬细胞（BMDM），导致 iNOS、IL-6、IL-10 和 TNF-α 的表达出现差异。此外，先前用腹腔 B-1 细胞释放的 EVs 处理的 BALB/c 小鼠，其病变大小和寄生虫负荷明显降低。因此，本研究表明，腹腔 B-1 细胞可以释放 EVs，从而改变体外巨噬细胞的功能，并且这些 EVs 改变了 L. amazonensis 感染的进程。这些发现代表了第一个证据，即来自腹腔 B-1 细胞的 EVs 可以作为巨噬细胞和 B-1 细胞之间细胞通讯的新机制，有助于对实验性利什曼病的免疫。
