Fungal dissemination is limited by liver macrophage filtration of the blood
Fungal dissemination is limited by liver macrophage filtration of the blood
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DOI：
10.1038/s41467-019-12381-5
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发表时间：
2019-10-08
影响因子：
16.6
通讯作者：
Shi, Meiqing
中科院分区：
文献类型：
--
作者：
Sun, Donglei;Sun, Peng;Shi, Meiqing
真菌传播到血液中是导致侵袭性真菌感染的关键步骤。在这里，使用活体成像，我们表明，枯否细胞（KCs）在肝脏中有一个突出的功能，在捕获循环的新型隐球菌和白色念珠菌，从而减少真菌传播到靶器官。补体C3而非C5和补体受体CRIg而非CR 3参与C的捕获。新人类C的内化。KC对新生儿的作用随后由多种受体介导，包括CR 3、CRIg和清道夫受体，这些受体与C5 aR信号传导沿着协同作用。吞噬后，C. KCs以IFN-γ非依赖性方式抑制新生儿。因此，肝过滤器通过KC传播循环中的真菌，为肝病个体中隐球菌病风险增加提供了机制解释，并提出了通过增强KC功能来预防真菌传播的治疗策略。
Fungal dissemination into the bloodstream is a critical step leading to invasive fungal infections. Here, using intravital imaging, we show that Kupffer cells (KCs) in the liver have a prominent function in the capture of circulating Cryptococcus neoformans and Candida albicans, thereby reducing fungal dissemination to target organs. Complement C3 but not C5, and complement receptor CRIg but not CR3, are involved in capture of C. neoformans. Internalization of C. neoformans by KCs is subsequently mediated by multiple receptors, including CR3, CRIg, and scavenger receptors, which work synergistically along with C5aR signaling. Following phagocytosis, the growth of C. neoformans is inhibited by KCs in an IFN-gamma independent manner. Thus, the liver filters disseminating fungi from circulation via KCs, providing a mechanistic explanation for the enhanced risk of cryptococcosis among individuals with liver diseases, and suggesting a therapeutic strategy to prevent fungal dissemination through enhancing KC functions.