TLRs和NLRs协同影响胸膜肺炎放线杆菌诱导的胸膜肺炎IRFs的表达
湖南农业大学, 动物医学院, 湖南长沙 410128
| 摘 要： | 猪传染性胸膜肺炎是由胸膜肺炎放线杆菌感染而引起的一种猪的重要传染病，NLRs和TLRs可能参与了猪传染性胸膜肺炎的发生。研究表明，IRFs在调节感染过程中的炎症因子表达从而调节炎症的发生和机体的抗菌反应其重要作用，为探讨它们在猪传染性胸膜肺炎肺部病变发生中的作用，我们在App经滴鼻感染制造胸膜肺炎放线杆菌小鼠模型的基础上，利用石蜡切片检测了小鼠的肺部病变，同时利用qPCR和western-blot检测多个基因表达的变化。结果表明，小鼠经滴鼻感染App 48 h后出现呼吸困难、厌食等症状。尸检发现急性出血性肺炎对肺造成严重损伤。组织病理变化以出血、嗜酸性粒细胞及淋巴细胞浸润为特征。与对照组比较，App感染小鼠肺组织中白细胞介素-8 (IL-8)、IL-10、IL-1β、IL-6、干扰素-α(INF-α)、toll样受体-2(TLR-2)、TLR-4、干扰素调节因子-1(IRF-1)、IRF-5、IRF-7、NLRP-3表达显著升高，而IRF-3、IRF-4表达显著降低（P<0.05或P<0.01）。本研究提示TLR/NLRs信号通路可能协同激活App诱导的小鼠胸膜肺炎模型中的IRFs的表达，进而调节小鼠肺部的炎症反应和肺部炎症。 |
| 关 键 词： | 小鼠; 胸膜肺炎放线杆菌; 致炎因子; IRF; NLRP-3炎性小体 |
| DOI： | 10.57237/j.life.2022.01.001 |
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收稿日期: 2022-08-28
接受日期: 2022-10-05
在线出版日期: 2022-12-15
TLR and NLRs Signaling May Synergistically Affect Expression of IRFs in Mouse Pleuropneumonia Model Induced by Actinobacillus pleuropneumoniae
College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China
| Abstract: | Porcine contagious pleuropneumonia, caused by Actinobacillus pleuropneumoniae (App), is a very important disease in pig industry. NLRs and TLRs may involve in the pathogenesis of this disease. It was reported that IRFs played an important role in regulating the expression of inflammatory factors during infectious diseases, thus regulating the occurrence of inflammation and the antibacterial reaction, In order to investigate their role in the pathogenesis of pulmonary lesions in porcine contagious pleuropneumonia, we employed a mouse model of intranasal infection by App, which resulted in lung inflammation. Mice showed dyspnea and anorexia after intranasal inoculation with App at post-inoculation 48 h. In the autopsy, the lungs were found to be severely damaged by acute hemorrhagic pneumonia. The histopathologic changes were characterized by hemorrhage, eosnophils and lymphocyte infiltration. Expression of interleukin-8 (IL-8), IL-10, IL-1β、IL-6, interferon-α(INF-α), toll-like receptor-2 (TLR-2), TLR-4, interferon regulatory factor-1(IRF-1), IRF-5, IRF-7, and NLRP-3 were increased significantly concomitantly with decreased expression of IRF-3 and IRF-4 in the lung of App infected mice compared with control (P<0.05 or P<0.01). The present results suggest that TLR/NLRs signaling may synergistically activate IRFs in mouse pleuropneumonia model induced by App and then regulate the inflammatory response and lung inflammation in mice. |
| Keywords: | Mice; Actinobacillus pleuropneumonia; Preinflammatory Cytokines; IRF; NLRP-3 Inflammasome |
基金
| 1. | 湖南省教育厅重点项目资助 (No. 16A101). |
参考文献
| [1] | Högbom M, Ihalin R. Functional and structural characteristics of bacterial proteins that bind host cytokines. Virulence. 2017, 8 (8): 1592-1601. |
| [2] | Imanishi J. Expression of cytokines in bacterial and viral infections and their biochemical aspects [J]. J Biochem. 2000, 127 (4): 525-530. |
| [3] | Shaabani N, Vartabedian VF, Nguyen N, et al. IFN-β, but not IFN-α, is responsible for the pro-Bacterial Effect of Type I interferon. Cell Physiol Biochem. 2021, 55 (3): 256-264. |
| [4] | Paludan SR. Innate antiviral defenses independent of inducible IFNα/βproduction [J]. Trends Immunol. 2016, 37 (9): 588-596. |
| [5] | McNab F, Mayer-Barber K, Sher A, et al. Type I interferons in infectious disease [J]. Nat Rev Immunol. 2015, 15 (2): 87-103. |
| [6] | Bajpai A, Prasad KN, Mishra P, et al. Distinct cytokine pattern in response to different bacterial pathogens in human brain abscess [J]. J Neuroimmunol. 2014, 273 (1-2): 96-102. |
| [7] | Wang X, Gu W, Qiu H, et al. Comparison of the cytokine immune response to pathogenic Yersinia enterocolitica bioserotype 1B/O:8 and 2/O:9 in susceptible BALB/C and resistant C57BL/6 mice [J]. Mol Immunol. 2013, 55 (3-4): 365-371. |
| [8] | Islam D, Lombardini E, Ruamsap N, et al. Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll-like receptor 4 antagonist [J]. Immunology. 2016, 147 (2): 178-189. |
| [9] | 张宇航, 黄复深. 猪传染性胸膜肺炎研究进展.黑龙江畜牧兽医. 2019, (13): 45-48. |
| [10] | Bossé JT, Janson H, Sheehan BJ, et al. Actinobacillus pleuropneumoniae: pathobiology and pathogenesis of infection [J]. Microbes Infect. 2002, 4 (2): 225-235. |
| [11] | Zuo Z, Cui H, Li M, et al. Transcriptional profiling of swine lung tissue after experimental infection with Actinobacillus pleuropneumoniae [J]. Int J Mol Sci. 2013, 14 (5): 10626-10660. |
| [12] | 胡佩佩, 黄复深, 牛俊超, 等. 猪胸膜肺炎放线杆菌感染小鼠所致炎症中TLR-4信号通路涉及细胞焦亡 [J]. 微生物学报, 2015, 55 (05): 650-656. |
| [13] | Oviedo-Boyso J, Bravo-Patiño A, Baizabal-Aguirre VM. Collaborative action of Toll-like and NOD-like receptors as modulators of the inflammatory response to pathogenic bacteria [J]. Mediators Inflamm. 2014, 2014: 432785. |
| [14] | Zhao J, Chen C, Xiao JR, et al. An Up-regulation of IRF-1 after a spinal cord injury: implications for neuronal apoptosis [J]. J Mol Neurosci. 2015, 57 (4): 595-604. |
| [15] | Monroe KM, McWhirter SM, Vance RE. Induction of type I interferons by bacteria [J]. Cell Microbiol. 2010, 12 (7): 881-890. |
| [16] | Zhou Y, Li S, Tang Z, et al. Different antiviral effects of IFNα and IFNβ in an HBV mouse model [J]. Immunobiology. 2017, 222 (3): 562-570. |
| [17] | Sheehan KC, Lazear HM, Diamond MS, et al. Selective blockade of interferon-α and -β reveals their non-Redundant functions in a mouse model of West Nile Virus infection [J]. PLoS One. 2015, 10 (5): e0128636. |
| [18] | Chen W, Royer WE Jr. Structural insights into interferon regulatory factor activation [J]. Cell Signal. 2010, 22 (6): 883-887. |
| [19] | Dou L, Liang HF, Geller DA, et al. The regulation role of interferon regulatory factor-1 gene and clinical relevance [J]. Hum Immunol. 2014, 75 (11): 1110-1114. |
| [20] | Puthia M, Ambite I, Cafaro C, et al. IRF7 inhibition prevents destructive innate immunity-A target for nonantibiotic therapy of bacterial infections [J]. Sci Transl Med. 2016, 8 (336): 336ra59. |
| [21] | Savitsky D, Tamura T, Yanai H, et al. Regulation of immunity and oncogenesis by the IRF transcription factor family [J]. Cancer Immunol Immunother. 2010, 59 (4): 489-510. |
| [22] | Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity [J]. Immunity. 2011, 34 (5): 637-650. |
| [23] | Coveney AP, Wang W, Kelly J, et al. Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways [J]. Sci Rep. 2015, 5:13694. |
| [24] | Ramstead AG, Robison A, Blackwell A, et al. Roles of Toll-Like receptor 2 (TLR2), TLR4, and MyD88 during pulmonary coxiella burnetii infection. Infect Immun [J]. 2016, 84 (4): 940-949. |
| [25] | Koch KN, Müller A. Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens [J]. Gut Microbes. 2015, 6 (6): 382-387. |
| [26] | Netea MG, Ferwerda G, de Jong DJ, et al. Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release [J]. J Immunol. 2005, 174 (10): 6518-6523. |
| [27] | Guzelj S, Jakopin Ž. Nucleotide-Binding oligomerization domain 1/Toll-Like Receptor 4 co-Engagement promotes non-specific immune response against K562 cancer cells. Front Pharmacol. 2022, 13: 920928. |
| [28] | Kim JJ, Jo EK. NLRP3 inflammasome and host protection against bacterial infection [J]. J Korean Med Sci. 2013, 28 (10): 1415-1423. |
| [29] | Colonna M. TLR pathways and IFN-regulatory factors: to each its own [J]. Eur J Immunol. 2007, 37 (2): 306-309. |
