Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells
Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells
复制标题
DOI：
10.1128/iai.00330-21
复制
发表时间：
2021-10-01
影响因子：
3.1
通讯作者：
Kawakami, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Kitai, Yuki;Sato, Ko;Kawakami, Kazuyoshi
新型隐球菌是一种酵母型真菌病原体，其细胞壁和荚膜富含多糖。Dectin-2是一种识别高甘露糖多糖的C型凝集素受体（Receptor，RECEPTIN）。以前，我们证明了Dectin-2参与了骨髓来源的树突状细胞（BM-DCs）对C.新人类在本研究中，我们分析了Dectin-2在C. BM-DCs的新型人。与野生型（WT）小鼠相比，在缺乏Dectin-2（Dectin-2敲除（Dectin-2KO））或含有半胱天冬酶募集结构域的蛋白9（CARD 9 KO）的小鼠中，BM-DCs对该真菌的吞噬显著降低，CARD 9 KO是一种传递由CLR触发的信号的常见衔接子分子。通过抑制Syk（一种参与CLR触发激活的信号分子），吞噬作用也受到类似程度的抑制。相反，PI 3 K抑制剂完全消除了C.新人类肌动蛋白聚合，即，在与C.在Dectin-2KO和CARD 9 KO小鼠的BM-DCs中，新生儿的BM-DCs也减少。最后，C.与WT小鼠相比，在Dectin-2KO小鼠的肺中，巨噬细胞对新生儿的吞噬作用显著降低。这些结果表明，Dectin-2可能在C.可能通过CARD 9信号传导和Syk和PI 3 K介导的信号传导途径。
The cell walls and capsules of Cryptococcus neoformans, a yeast-type fungal pathogen, are rich in polysaccharides. Dectin-2 is a C-type lectin receptor (CLR) that recognizes high-mannose polysaccharides. Previously, we demonstrated that Dectin-2 is involved in cytokine production by bone marrow-derived dendritic cells (BM-DCs) in response to stimulation with C. neoformans. In the present study, we analyzed the role of Dectin-2 in the phagocytosis of C. neoformans by BM-DCs. The engulfment of this fungus by BM-DCs was significantly decreased in mice lacking Dectin-2 (Dectin-2 knockout (Dectin-2KO)) or caspase recruitment domain-containing protein 9 (CARD9KO), a common adapter molecule that delivers signals triggered by CLRs, compared to wild-type (WT) mice. Phagocytosis was likewise inhibited, to a similar degree, by the inhibition of Syk, a signaling molecule involved in CLR-triggered activation. A PI3K inhibitor, in contrast, completely abrogated the phagocytosis of C. neoformans. Actin polymerization, i.e., conformational changes in cytoskeletons detected at sites of contact with C. neoformans, was also decreased in BM-DCs of Dectin-2KO and CARD9KO mice. Finally, the engulfment of C. neoformans by macrophages was significantly decreased in the lungs of Dectin-2KO mice compared to WT mice. These results suggest that Dectin-2 may play an important role in the actin polymerization and phagocytosis of C. neoformans by DCs, possibly through signaling via CARD9 and a signaling pathway mediated by Syk and PI3K.