Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an <i>in vivo</i> hACE2 transfection mouse model

Yan Liang; Heng Li; Jing Li; Ze-Ning Yang; Jia-Li Li; Hui-Wen Zheng; Yan-Li Chen; Hai-Jing Shi; Lei Guo; Long-Ding Liu

doi:10.24272/j.issn.2095-8137.2020.118

Volume 41 Issue 6

Nov. 2020

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Article Navigation > Zoological Research > 2020 > 41(6): 621-631

Yan Liang, Heng Li, Jing Li, Ze-Ning Yang, Jia-Li Li, Hui-Wen Zheng, Yan-Li Chen, Hai-Jing Shi, Lei Guo, Long-Ding Liu. Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model. Zoological Research, 2020, 41(6): 621-631. doi: 10.24272/j.issn.2095-8137.2020.118

Citation:

Yan Liang, Heng Li, Jing Li, Ze-Ning Yang, Jia-Li Li, Hui-Wen Zheng, Yan-Li Chen, Hai-Jing Shi, Lei Guo, Long-Ding Liu. Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model. Zoological Research, 2020, 41(6): 621-631. doi: 10.24272/j.issn.2095-8137.2020.118

Citation:

Yan Liang, Heng Li, Jing Li, Ze-Ning Yang, Jia-Li Li, Hui-Wen Zheng, Yan-Li Chen, Hai-Jing Shi, Lei Guo, Long-Ding Liu. Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model. Zoological Research, 2020, 41(6): 621-631. doi: 10.24272/j.issn.2095-8137.2020.118

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Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model

doi: 10.24272/j.issn.2095-8137.2020.118

Yan Liang^{1, #},
Heng Li^{1, #},
Jing Li^{1, #},
Ze-Ning Yang¹,
Jia-Li Li¹,
Hui-Wen Zheng¹,
Yan-Li Chen¹,
Hai-Jing Shi¹,
Lei Guo^{1
,
,},
Long-Ding Liu^{1
,
,}

1.
Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, Yunnan 650118, China

#Authors contributed equally to this work

Funds: This work was supported by the National Natural Science Foundation of China (82041017) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2016-I2M-1-014)

More Information

Corresponding author: E-mail: shried@163.com; longdingl@gmail.com
Received Date: 2020-05-14
Published Online: 2020-10-12
Publish Date: 2020-11-18

Abstract

Abstract

Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals. Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation. However, normal adult mice are not susceptible to SARS-CoV-2. Here, we developed a viral receptor (human angiotensin-converting enzyme 2, hACE2) pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung. Based on the model, the virus successfully infected the mouse lung 2 days after transfection. Viral RNA/protein, innate immune cell infiltration, inflammatory cytokine expression, and pathological changes in the infected lungs were observed after infection. Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection. In addition, using infected CXCL5-knockout mice, chemokine CXCL5 was responsible for neutrophil recruitment. CXCL5 knockout decreased lung inflammation without diminishing viral clearance, suggesting a potential target for controlling pneumonia.
- SARS-CoV-2,
- Mouse model,
- Lung infection,
- ACE2,
- Neutrophil,
- CXCL5

#Authors contributed equally to this work

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References(35)

References

[1]	Baggiolini M, Dewald B, Moser B. 1993. Lnterleukin-8 and related chemotactic cytokines–CXC and CC chemokines. Advances in Immunology, 55: 97−179. doi: 10.1016/S0065-2776(08)60509-X
[2]	Balamayooran G, Batra S, Cai SS, Mei JJ, Worthen GS, Penn AL, et al. 2012. Role of CXCL5 in leukocyte recruitment to the lungs during secondhand smoke exposure. American Journal of Respiratory Cell and Molecular Biology, 47(1): 104−111. doi: 10.1165/rcmb.2011-0260OC
[3]	Balamayooran G, Batra S, Fessler MB, Happel KI, Jeyaseelan S. 2010. Mechanisms of neutrophil accumulation in the lungs against bacteria. American Journal of Respiratory Cell and Molecular Biology, 43(1): 5−16. doi: 10.1165/rcmb.2009-0047TR
[4]	Bao LL, Deng W, Huang BY, Gao H, Liu JN, Ren LL, et al. 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature, 583(7818): 830−833. doi: 10.1038/s41586-020-2312-y
[5]	Chan JFW, Zhang AJ, Yuan SF, Poon VKM, Chan CCS, Lee ACY, et al. 2020. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in a golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clinical Infectious Diseases: ciaa325.
[6]	Chen SC, Mehrad B, Deng JC, Vassileva G, Manfra DJ, Cook DN, et al. 2001. Impaired pulmonary host defense in mice lacking expression of the CXC chemokine lungkine. The Journal of Immunology, 166(5): 3362−3368. doi: 10.4049/jimmunol.166.5.3362
[7]	Das S, MacDonald K, Chang HYS, Mitzner W. 2013. A simple method of mouse lung intubation. Journal of Visualized Experiments, (73): e50318.
[8]	Deng W, Bao LL, Liu JN, Xiao C, Liu JY, Xue J, et al. 2020. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science, 369(6505): 818−823. doi: 10.1126/science.abc5343
[9]	Driscoll KE, Hassenbein DG, Howard BW, Isfort RJ, Cody D, Tindal MH, et al. 1995. Cloning, expression, and functional characterization of rat MIP-2: a neutrophil chemoattractant and epithelial cell mitogen. Journal of Leukocyte Biology, 58(3): 359−364. doi: 10.1002/jlb.58.3.359
[10]	Frevert CW, Huang S, Danaee H, Paulauskis JD, Kobzik L. 1995. Functional characterization of the rat chemokine KC and its importance in neutrophil recruitment in a rat model of pulmonary inflammation. Journal of Immunology, 154(1): 335−344.
[11]	Guo L, Feng K, Wang YC, Mei JJ, Ning RT, Zheng HW, et al. 2017. Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection. Mucosal Immunology, 10(6): 1529−1541. doi: 10.1038/mi.2017.1
[12]	Huang CL, Wang YM, Li XW, Ren LL, Zhao JP, Hu Y, et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223): 497−506. doi: 10.1016/S0140-6736(20)30183-5
[13]	Jiang RD, Liu MQ, Chen Y, Shan C, Zhou YW, Shen XR, et al. 2020. Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell, 182(1): 50−58.e8. doi: 10.1016/j.cell.2020.05.027
[14]	Li WH, Moore MJ, Vasilieva N, Sui JH, Wong SK, Berne MA, et al. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 426(6965): 450−454. doi: 10.1038/nature02145
[15]	Lu SY, Zhao Y, Yu WH, Yang Y, Gao JH, Wang JB, et al. 2020. Comparison of nonhuman primates identified the suitable model for COVID-19. Signal Transduction and Targeted Therapy, 5(1): 157. doi: 10.1038/s41392-020-00269-6
[16]	Lukacs NW, Hogabaom C, Campbell E, Kunkel SL. 1999. Chemokines: function, regulation and alteration of inflammatory responses. Chemical Immunology, 72: 102−120. doi: 10.1159/000058729
[17]	McCray PB Jr, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. 2007. Lethal infection of K18-hACE2 mice infected with wevere acute respiratory sundrome coronavirus. Journal of Virology, 81(2): 813−821. doi: 10.1128/JVI.02012-06
[18]	Mei JJ, Liu YH, Dai N, Favara M, Greene T, Jeyaseelan S, et al. 2010. CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity, 33(1): 106−117. doi: 10.1016/j.immuni.2010.07.009
[19]	Moore JB, June CH. 2020. Cytokine release syndrome in severe COVID-19. Science, 368(6490): 473−474. doi: 10.1126/science.abb8925
[20]	Puneet P, Moochhala S, Bhatia M. 2005. Chemokines in acute respiratory distress syndrome. American Journal of Physiology - Lung Cellular and Molecular Physiology, 288(1): L3−L15. doi: 10.1152/ajplung.00405.2003
[21]	Qin C, Zhou LQ, Hu ZW, Zhang SQ, Yang S, Tao Y, et al. 2020. Dysregulation of immune response in patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clinical Infectious Diseases, 71(15): 762−768. doi: 10.1093/cid/ciaa248
[22]	Read LJ, Muench H. 1938. A simple method of estimating fifty percent endpoints. American Journal of Epidemiology, 27: 493−497. doi: 10.1093/oxfordjournals.aje.a118408
[23]	Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, et al. 2020. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science, 368(6949): 1012−1015.
[24]	Shan C, Yao YF, Yang XL, Zhou YW, Gao G, Peng Y, et al. 2020. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Cell Research, 30(8): 670−677. doi: 10.1038/s41422-020-0364-z
[25]	Shi JZ, Wen ZY, Zhong GX, Yang HL, Wang C, Huang BY, et al. 2020. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science, 368(6494): 1016−1020. doi: 10.1126/science.abb7015
[26]	Song TZ, Zheng HY, Han JB, Jin L, Yang X, Liu FL, et al. 2020. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 41(5): 503−516. doi: 10.24272/j.issn.2095-8137.2020.202
[27]	Sun J, Zhuang Z, Zheng J, Li K, Wong RLY, Liu DL, et al. 2020. Generation of a broadly useful model for COVID-19 pathogenesis, vaccination, and treatment. Cell, 182(3): 734−743. doi: 10.1016/j.cell.2020.06.010
[28]	Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC. 2009. Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. The Journal of Immunology, 183(11): 7441−7450. doi: 10.4049/jimmunol.0902497
[29]	Tseng CTK, Huang C, Newman P, Wang N, Narayanan K, Watts DM, et al. 2007. Severe acute respiratory syndrome coronavirus infection of mice transgenic for the human Angiotensin-converting enzyme 2 virus receptor. Journal of Virology, 81(3): 1162−1173. doi: 10.1128/JVI.01702-06
[30]	Xu L, Yu DD, Ma YH, Yao YL, Luo RH, Feng XL, et al. 2020a. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 41(5): 517−526. doi: 10.24272/j.issn.2095-8137.2020.053
[31]	Xu Z, Shi L, Wang YJ, Zhang JY, Huang L, Zhang C, et al. 2020b. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine, 8(4): 420−422. doi: 10.1016/S2213-2600(20)30076-X
[32]	Yang XH, Deng W, Tong Z, Liu YX, Zhang LF, Zhu H, et al. 2007. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comparative Medicine, 57(5): 450−459.
[33]	Zhang YN, Li XD, Zhang ZR, Zhang HQ, Li N, Liu J, et al. 2020. A mouse model for SARS-CoV-2 infection by exogenous delivery of hACE2 using alphavirus replicon particles. Cell Research. doi: 10.1038/s41422-020-00405-5.
[34]	Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798): 270−273. doi: 10.1038/s41586-020-2012-7
[35]	Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. 2020. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell, 181(5): 1016−1035. doi: 10.1016/j.cell.2020.04.035