Nitric Oxide-Induced Calcineurin A Mediates Antimicrobial Peptide Production Through the IMD Pathway.
Nitric Oxide-Induced Calcineurin A Mediates Antimicrobial Peptide Production Through the IMD Pathway.
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一氧化氮诱导的钙调神经磷酸酶 A 通过 IMD 途径介导抗菌肽的产生
DOI：
10.3389/fimmu.2022.905419
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发表时间：
2022
影响因子：
7.3
通讯作者：
Feng, Congjing
中科院分区：
文献类型：
--
作者：
Chen, Kangkang;Wang, Xinyan;Wei, Xiangyi;Chen, Jiaqian;Wei, Youheng;Jiang, Haobo;Lu, Zhiqiang;Feng, Congjing
关键词：
一氧化氮(NO)在高浓度时是昆虫免疫反应中杀死病原体的效应物，在低浓度时也是调节昆虫体内抗菌肽(AMP)产生的第二信使。果蝇钙调神经磷酸酶亚单位CanA1是一种普遍存在的丝氨酸/苏氨酸蛋白磷酸酶，参与NO诱导的AMP的产生。然而，目前尚不清楚NO如何调控AMP的表达。在本研究中，我们利用鳞翅目害虫玉米象和果蝇S2细胞来研究NO信号对AMP产生的影响。细菌感染可上调幼虫血淋巴中一氧化氮合酶1/2(NOS1/2)、CANA和AMP基因的转录，增加血淋巴中NO的浓度。抑制NOS或CANA活性降低了感染细菌的亚洲玉米象的存活率。NO供体增加血浆中NO水平，并上调CANA和某些AMP的产生。在S2细胞中，灭活大肠杆菌可诱导一氧化氮合酶的转录，促进一氧化氮的产生，而一氧化氮合酶的敲除则阻断了大肠杆菌引起的一氧化氮水平的升高。与亚洲玉米象幼虫一样，补充NO供体可增加培养上清液中的NO水平和S2细胞中AMP的表达。对关键途径基因的抑制表明，IMD(而不是Toll)途径参与了致死的大肠杆菌上调CecropinA1、防御素、敌百虫和屈曲霉素的过程。敲除一氧化氮合酶还可降低大肠杆菌诱导的CANA1和AMP的表达，表明NO在AMP的表达中起作用。此外，CanA1 RNA干扰和抑制其磷酸酶活性显著降低了NO诱导的AMP表达，而敲除IMD则抑制了NO诱导的AMP表达。综上所述，这些结果表明，NO诱导的AMP的产生是由CanA1通过IMD途径介导的。
Nitric oxide (NO) at a high concentration is an effector to kill pathogens during insect immune responses, it also functions as a second messenger at a low concentration to regulate antimicrobial peptide (AMP) production in insects. Drosophila calcineurin subunit CanA1 is a ubiquitous serine/threonine protein phosphatase involved in NO-induced AMP production. However, it is unclear how NO regulates AMP expression. In this study, we used a lepidopteran pest Ostrinia furnacalis and Drosophila S2 cells to investigate how NO signaling affects the AMP production. Bacterial infections upregulated the transcription of nitric oxide synthase 1/2 (NOS1/2), CanA and AMP genes and increased NO concentration in larval hemolymph. Inhibition of NOS or CanA activity reduced the survival of bacteria-infected O. furnacalis. NO donor increased NO level in plasma and upregulated the production of CanA and certain AMPs. In S2 cells, killed Escherichia coli induced NOS transcription and boosted NO production, whereas knockdown of NOS blocked the NO level increase caused by E. coli. As in O. furnacalis larvae, supplementation of the NO donor increased NO level in the culture medium and AMP expression in S2 cells. Suppression of the key pathway genes showed that the IMD (but not Toll) pathway was involved in the upregulation of CecropinA1, Defensin, Diptericin, and Drosomycin by killed E. coli. Knockdown of NOS also reduced the expression of CanA1 and AMPs induced by E. coli, indicative of a role of NO in the AMP expression. Furthermore, CanA1 RNA interference and inhibition of its phosphatase activity significantly reduced NO-induced AMP expression, and knockdown of IMD suppressed NO-induced AMP expression. Together, these results suggest that NO-induced AMP production is mediated by CanA1 via the IMD pathway.
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影响因子：
2.9
作者：
Hillyer, Julian F.;Estevez-Lao, Tania Y.
通讯作者：
Estevez-Lao, Tania Y.
影响因子：
--
作者：
Ganesan, Sandhya;Aggarwal, Kamna;Paquette, Nicholas;Silverman, Neal
通讯作者：
Silverman, Neal
DOI：
10.1073/pnas.070357597
发表时间：
2000-03-28
影响因子：
11.1
作者：
Basset, A;Khush, RS;Lemaitre, B
通讯作者：
Lemaitre, B
影响因子：
2.9
作者：
Chen, Kangkang;Lu, Zhiqiang
通讯作者：
Lu, Zhiqiang
影响因子：
9.3
作者：
Furman JL;Norris CM
通讯作者：
Norris CM