Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans
Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans
复制标题
DOI：
10.1128/iai.00400-20
复制
发表时间：
2020-08
影响因子：
3.1
通讯作者：
Yukio Sato;Ko Sato;Hideki Yamamoto;J. Kasamatsu;T. Miyasaka;D. Tanno;Anna Miyahara;Takafumi Kagesawa;Akiho Oniyama;K. Kawamura;Rin Yokoyama;Yuki Kitai;Aya Umeki;Shigenari Ishizuka;K. Takano;Ryuhei Shiroma;Nana Nakahata;K. Kawakami;E. Kanno;H. Tanno;S. Yamasaki;H. Hara;K. Ishii;K. Kawakami
中科院分区：
文献类型：
--
作者：
Yukio Sato;Ko Sato;Hideki Yamamoto;J. Kasamatsu;T. Miyasaka;D. Tanno;Anna Miyahara;Takafumi Kagesawa;Akiho Oniyama;K. Kawamura;Rin Yokoyama;Yuki Kitai;Aya Umeki;Shigenari Ishizuka;K. Takano;Ryuhei Shiroma;Nana Nakahata;K. Kawakami;E. Kanno;H. Tanno;S. Yamasaki;H. Hara;K. Ishii;K. Kawakami
隐球菌是一种机会性真菌病原体，经常引起致命的脑膜脑炎患者的细胞介导的免疫反应受损，如艾滋病。caspase相关募集结构域9 （CARD9）在宿主对隐球菌感染的防御中起关键作用，表明一种或多种c型凝集素受体（CLRs）参与其中。在本研究中，我们分析了巨噬细胞诱导的c型凝集素（Mincle）在宿主防御巨噬细胞感染中的作用。隐球菌是一种机会性真菌病原体，在细胞介导的免疫反应受损（如艾滋病）患者中经常引起致命性脑膜脑炎。caspase相关募集结构域9 （CARD9）在宿主对隐球菌感染的防御中起关键作用，表明一种或多种c型凝集素受体（CLRs）参与其中。在本研究中，我们分析了巨噬细胞诱导的c型凝集素（Mincle）在宿主防御巨噬细胞感染中的作用。野生型（WT）小鼠肺部的Mincle表达在隐球菌感染早期以card9依赖的方式增加。在Mincle基因破坏（Mincle KO）小鼠中，这种真菌的清除率、病理结果、Th1/Th2反应和感染肺部的抗菌肽产生几乎与WT小鼠相当。然而，与WT小鼠相比，Mincle KO小鼠肺中白细胞介素-22 （IL-22）、肿瘤坏死因子α (TNF-α)和IL-6的产生以及AhR的表达均显著降低。在体外实验中，Mincle KO小鼠骨髓源性树突状细胞产生的TNF-α明显减少。此外，在活化T细胞（NFAT）核因子-表达该受体的绿色荧光蛋白（GFP）报告细胞的实验中，被破坏的C. deeoformans裂解物，而不是整个酵母细胞，激活了mincle触发的信号。这些结果表明，Mincle可能参与隐球菌感染早期th22相关细胞因子的产生，尽管它在宿主防御隐球菌感染中的作用可能有限。
Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. ABSTRACT Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of interleukin-22 (IL-22), tumor necrosis factor alpha (TNF-α), and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to those of WT mice. In in vitro experiments, TNF-α production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not those of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.