Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways.
Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways.
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DOI：
10.1038/s41467-022-32405-x
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发表时间：
2022-08-18
影响因子：
16.6
通讯作者：
Zhang, Xianlong
中科院分区：
文献类型：
--
作者：
Yang, Chuang;Luo, Yao;Shen, Hao;Ge, Min;Tang, Jin;Wang, Qiaojie;Lin, Han;Shi, Jianlin;Zhang, Xianlong
操纵免疫细胞共抑制或共激活信号的策略已经彻底改变了免疫疗法。然而，某些免疫学上的冷疾病，例如医疗植入物的细菌生物膜感染，由于所涉及的免疫共刺激途径的复杂性而难以靶向。在这里，我们表明，二维锰硫族磷酸盐MnPSe 3（MPS）纳米片改性与聚乙烯吡咯烷酮（PVP）能够触发一个强大的抗细菌生物膜体液免疫小鼠模型的外科植入物感染，通过调节抗原呈递和共刺激分子的表达在感染微环境（IME）。从机制上讲，PVP修饰的MPS（MPS-PVP）破坏生物膜的结构，通过产生反应性氧化物质导致抗原暴露，同时改变免疫抑制（IL 4 I1和CD 206）和共激活因子信号（CD 40、CD 80和CD 69）的平衡。这导致扩增的APC引发和抗原呈递，导致生物膜特异性体液免疫和记忆应答。在我们的工作中，我们证明利用MPS-PVP的术前新辅助免疫治疗成功减轻了取出受感染植入物后的残留和复发感染。因此，这项研究提供了一种替代抗生素治疗难以治疗的生物膜感染的方法。细菌生物膜形成是外科植入的主要风险，并且需要移除植入物和积极的抗生素治疗。在这里，作者表明，手术后应用含锰无机纳米片通过改善抗原呈递和针对生物膜的体液免疫应答来减少残留和复发感染。
Strategies to manipulate immune cell co-inhibitory or co-activating signals have revolutionized immunotherapy. However, certain immunologically cold diseases, such as bacterial biofilm infections of medical implants are hard to target due to the complexity of the immune co-stimulatory pathways involved. Here we show that two-dimensional manganese chalcogenophosphates MnPSe3 (MPS) nanosheets modified with polyvinylpyrrolidone (PVP) are capable of triggering a strong anti-bacterial biofilm humoral immunity in a mouse model of surgical implant infection via modulating antigen presentation and costimulatory molecule expression in the infectious microenvironment (IME). Mechanistically, the PVP-modified MPS (MPS-PVP) damages the structure of the biofilm which results in antigen exposure by generating reactive oxidative species, while changing the balance of immune-inhibitory (IL4I1 and CD206) and co-activator signals (CD40, CD80 and CD69). This leads to amplified APC priming and antigen presentation, resulting in biofilm-specific humoral immune and memory responses. In our work, we demonstrate that pre-surgical neoadjuvant immunotherapy utilizing MPS-PVP successfully mitigates residual and recurrent infections following removal of the infected implants. This study thus offers an alternative to replace antibiotics against hard-to-treat biofilm infections. Bacterial biofilm formation is a major risk of surgical implantation, and necessitates implant removal and aggressive antibiotic treatment. Here authors show that post-surgical application of Manganese-containing inorganic nanosheets reduces residual and recurrent infection by improving antigen presentation and humoral immune response against the biofilms.
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影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.1038/s41577-019-0269-6
发表时间：
2020-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Irvine DJ;Dane EL
通讯作者：
Dane EL
影响因子：
5.3
作者：
Hsu, Yung-Heng;Hu, Chih-chien;Chang, Yuhan
通讯作者：
Chang, Yuhan
影响因子：
8.8
作者：
Carestia, Agostina;Mena, Hebe A.;Schattner, Mirta
通讯作者：
Schattner, Mirta
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R