PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow.
PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow.
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DOI：
10.1038/s41467-022-34722-7
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发表时间：
2022-11-11
影响因子：
16.6
通讯作者：
Jia, Xin-Ming
中科院分区：
文献类型：
--
作者：
Yu, Yao;Wang, Rong-Rong;Miao, Nai-Jun;Tang, Jia-Jie;Zhang, Yun-Wei;Lu, Xiang-Ran;Yan, Pei-Yi;Wang, Jing;Jia, Xin-Ming
程序性死亡配体1（PD-L1）已被证明在中性粒细胞上诱导表达，以抑制多微生物败血症、病毒和寄生虫感染期间的宿主免疫。然而，PD-L1对嗜中性粒细胞介导的抗真菌免疫的作用仍然完全未知。在这里，我们表明，在暴露于真菌病原体白色念珠菌酵母上的C型凝集素受体Dectin-1与其配体β-葡聚糖的接合后，小鼠和人类中性粒细胞上的PD-L1表达上调。此外，β-葡聚糖刺激诱导PD-L1易位到细胞核中以调节趋化因子CXCL 1和CXCL 2的产生，其控制中性粒细胞动员。重要的是，C。白念珠菌感染诱导的PD-L1表达通过介导中性粒细胞自分泌CXCL 1/2，导致中性粒细胞在骨髓中积聚。此外，嗜中性粒细胞特异性PD-L1缺陷损害了CXCL 1/2分泌，这促进了中性粒细胞从骨髓迁移到外周循环，从而赋予宿主对C.白色念珠菌感染最后，PD-L1阻断或PD-L1表达的药理学抑制显著增加了中性粒细胞从骨髓中的释放，以增强宿主抗真菌免疫力。我们的数据共同表明，β-葡聚糖对Dectin-1/PD-L1级联的激活抑制了中性粒细胞从骨髓储备中的释放，有助于抗真菌先天免疫的负调节，其作为针对危及生命的真菌感染的有效免疫靶点发挥作用。程序性死亡配体1（PD-L1）在感染和微生物脓毒症期间抑制宿主免疫。在这里，作者表明PD-L1通过调节CXCL 1和CXCL 2的分泌来控制白色念珠菌感染期间的中性粒细胞动员。
Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 on neutrophil-mediated antifungal immunity remains wholly unknown. Here, we show that the expression of PD-L1 on murine and human neutrophils was upregulated upon the engagement of C-type lectin receptor Dectin-1 with its ligand β-glucans, exposed on fungal pathogen Candida albicans yeast. Moreover, β-glucan stimulation induced PD-L1 translocation into nucleus to regulate the production of chemokines CXCL1 and CXCL2, which control neutrophil mobilization. Importantly, C. albicans infection-induced expression of PD-L1 leads to neutrophil accumulation in bone marrow, through mediating their autocrine secretion of CXCL1/2. Furthermore, neutrophil-specific deficiency of PD-L1 impaired CXCL1/2 secretion, which promoted neutrophil migration from bone marrow into the peripheral circulation, thereby conferring host resistance to C. albicans infection. Finally, either PD-L1 blockade or pharmacological inhibition of PD-L1 expression significantly increased neutrophil release from bone marrow to enhance host antifungal immunity. Our data together indicate that activation of Dectin-1/PD-L1 cascade by β-glucans inhibits neutrophil release from bone marrow reserve, contributing to the negative regulation of antifungal innate immunity, which functions as a potent immunotherapeutic target against life-threatening fungi infections. Programmed death ligand 1 (PD-L1) suppresses host immunity during infection and microbial sepsis. Here, the authors show that PD-L1 does this by regulating the secretion of CXCL1 and CXCL2 to control neutrophil mobilization during Candida albicans infection.
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影响因子：
7.3
作者：
da Fonseca-Martins AM;de Souza Lima-Gomes P;Antunes MM;de Moura RG;Covre LP;Calôba C;Rocha VG;Pereira RM;Menezes GB;Gomes DCO;Saraiva EM;de Matos Guedes HL
通讯作者：
de Matos Guedes HL
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
13.2
作者：
Deng W;Su Z;Liang P;Ma Y;Liu Y;Zhang K;Zhang Y;Liang T;Shao J;Liu X;Han W;Li R
通讯作者：
Li R
影响因子：
6.7
作者：
Altmeier S;Toska A;Sparber F;Teijeira A;Halin C;LeibundGut-Landmann S
通讯作者：
LeibundGut-Landmann S
影响因子：
6.7
作者：
Bowers NL;Helton ES;Huijbregts RP;Goepfert PA;Heath SL;Hel Z
通讯作者：
Hel Z