AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Home iRADIOLOGY Article
PDF (2.4 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review | Open Access

Advances in intravital imaging of liver immunity using optical microscopy and labeling methods

Xuenan Yuan1Xiang Yu2Bolei Dai1Zhihong Zhang1,2 ( )
Britton Chance Center and MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Huazhong University of Science and Technology, Wuhan, Hubei, China
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, Hainan, China
Show Author Information

Graphical Abstract

Abstract

The use of optical microscopy and labeling methods in intravital imaging allows for direct tracking of cell behavior and dynamic changes at the molecular level in the physiological or pathological microenvironment of living animals, revealing the spatiotemporal information of individual cells in the immune response. The liver is an immunological organ that contains unique innate and adaptive immune cells, including Kupffer cells (KCs) and different types of T cells, and is involved in coordinating multiple immune responses in the body. Using intravital imaging to visualize the movement behaviors and functions of immune cells during the reaction processes of the liver under physiological and pathological conditions has shed new light on the understanding of liver immunity, which is of great significance for the diagnosis and treatment of liver diseases. This review introduces various window models and labeling methods for the liver in intravital optical imaging and describes how it provides movement behavior and functional information about different types of immune cells, such as KCs and T cells, in the liver. Additionally, we highlight recent advances in intravital optical imaging of liver diseases, such as nonalcoholic fatty liver disease, infections, and tumors. This review aims to be a useful resource for comprehending the developments and achievements in intravital imaging of the liver and uncovering spatiotemporal information of immune response in a living microenvironment.

References

[1]

Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology (Baltimore, Md). 2006;43(2 Suppl 1): S54–62. https://doi.org/10.1002/hep.21060

[2]

Liu Z, Xu M, Huang S, Pan Q, Liu C, Zeng F, et al. Mesoscale visualization of three‐dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes. Theranostics. 2022;12(12): 5418–33. https://doi.org/10.7150/thno.71718

[3]

Huang S, Li B, Liu Z, Xu M, Lin D, Hu J, et al. Three‐dimensional mapping of hepatic lymphatic vessels and transcriptome profiling of lymphatic endothelial cells in healthy and diseased livers. Theranostics. 2023;13(2): 639–58. https://doi.org/10.7150/thno.79953

[4]

Medzhitov R, Janeway C, Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173(1): 89–97. https://doi.org/10.1034/j.1600‐065x.2000.917309.x

[5]

Kubes P, Jenne C. Immune responses in the liver. Annu Rev Immunol. 2018;36(1): 247–77. https://doi.org/10.1146/annurev‐immunol‐051116‐052415

[6]

Bourgognon M, Klippstein R, Al‐Jamal KT. Kupffer cell isolation for nanoparticle toxicity testing. Journal of visualized experiments : JoVE. 2015;102: e52989. https://doi.org/10.3791/52989

[7]

He JQ, Katschke KJ, Jr., Gribling P, Suto E, Lee WP, Diehl L, et al. CRIg mediates early Kupffer cell responses to adenovirus. J Leukoc Biol. 2013;93(2): 301–6. https://doi.org/10.1189/jlb.0612311

[8]

Heymann F, Peusquens J, Ludwig‐Portugall I, Kohlhepp M, Ergen C, Niemietz P, et al. Liver inflammation abrogates immunological tolerance induced by Kupffer cells. Hepatology (Baltimore, Md). 2015;62(1): 279–91. https://doi.org/10.1002/hep.27793

[9]

Bousso P, Bhakta NR, Lewis RS, Robey E. Dynamics of thymocyte‐stromal cell interactions visualized by two‐photon microscopy. Science (New York, NY). 2002;296(5574): 1876–80. https://doi.org/10.1126/science.1070945

[10]

Miller MJ, Wei SH, Parker I, Cahalan MD. Two‐photon imaging of lymphocyte motility and antigen response in intact lymph node. Science (New York, NY). 2002;296(5574): 1869–73. https://doi.org/10.1126/science.1070051

[11]

Stoll S, Delon J, Brotz TM, Germain RN. Dynamic imaging of T cell‐dendritic cell interactions in lymph nodes. Science (New York, NY). 2002;296(5574): 1873–6. https://doi.org/10.1126/science.1071065

[12]

Pittet MJ, Weissleder R. Intravital imaging. Cell. 2011;147(5): 983–91. https://doi.org/10.1016/j.cell.2011.11.004

[13]

Yi C, Zhu L, Li D, Fei P. Light field microscopy in biological imaging. J Innov Opt Health Sci. 2023;16(01): 2230017. https://doi.org/10.1142/s1793545822300178

[14]

Secklehner J, Lo Celso C, Carlin LM. Intravital microscopy in historic and contemporary immunology. Immunol Cell Biol. 2017;95(6): 506–13. https://doi.org/10.1038/icb.2017.25

[15]

Minsky M. Memoir on inventing the confocal scanning microscope. Scanning. 1988;10(4): 128–38. https://doi.org/10.1002/sca.4950100403

[16]

Jonkman J, Brown CM, Wright GD, Anderson KI, North AJ. Tutorial: guidance for quantitative confocal microscopy. Nat Protoc. 2020;15(5): 1585–611. https://doi.org/10.1038/s41596‐020‐0313‐9

[17]

Zipfel WR, Williams RM, Webb WW. Nonlinear magic: multiphoton microscopy in the biosciences. Nat Biotechnol. 2003;21(11): 1369–77. https://doi.org/10.1038/nbt899

[18]

Xu M, Wang LV. Photoacoustic imaging in biomedicine. Photoacoust Imag Biomed. 2006;77(4): 041101. https://doi.org/10.1063/1.2195024

[19]

Heymann F, Niemietz PM, Peusquens J, Ergen C, Kohlhepp M, Mossanen JC, et al. Long term intravital multiphoton microscopy imaging of immune cells in healthy and diseased liver using CXCR6.Gfp reporter mice. J Vis Exp: JoVE. 2015;97. https://doi.org/10.3791/52607‐v

[20]

Marques PE, Antunes MM, David BA, Pereira RV, Teixeira MM, Menezes GB. Imaging liver biology in vivo using conventional confocal microscopy. Nat Protoc. 2015;10(2): 258–68. https://doi.org/10.1038/nprot.2015.006

[21]

Babes L, Kubes P. Visualizing the tumor microenvironment of liver metastasis by spinning disk confocal microscopy. Methods Mol Biol. 2016;1458: 203–15.

[22]

Geissmann F, Cameron TO, Sidobre S, Manlongat N, Kronenberg M, Briskin MJ, et al. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol. 2005;3(4): e113. https://doi.org/10.1371/journal.pbio.0030113

[23]

Ritsma L, Steller EJ, Ellenbroek SI, Kranenburg O, Borel Rinkes IHM, van Rheenen J. Surgical implantation of an abdominal imaging window for intravital microscopy. Nat Protoc. 2013;8(3): 583–94. https://doi.org/10.1038/nprot.2013.026

[24]

Jacquemin G, Benavente‐Diaz M, Djaber S, Bore A, Dangles‐Marie V, Surdez D, et al. Longitudinal high‐resolution imaging through a flexible intravital imaging window. Sci Adv. 2021;7(25). https://doi.org/10.1126/sciadv.abg7663

[25]

Kuss MCA, Alimi OA, Hollingsworth MA, Duan B. Three‐dimensional printed abdominal imaging windows for in vivo imaging of deep‐lying tissues. Machines. 2022;10(8): 697. https://doi.org/10.3390/machines10080697

[26]

Deng D, Dai B, Wei J, Yuan X, Yang X, Qi S, et al. A drawer‐type abdominal window with an acrylic/resin coverslip enables long‐term intravital fluorescence/photoacoustic imaging of the liver. Nanophotonics. 2021;10(12): 3369–81. https://doi.org/10.1515/nanoph‐2021‐0281

[27]

Sakai M, Troutman TD, Seidman JS, Ouyang Z, Spann NJ, Abe Y, et al. Liver‐derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity. Immunity. 2019;51(4): 655–70.e8. https://doi.org/10.1016/j.immuni.2019.09.002

[28]

Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013;4(1): 2823. https://doi.org/10.1038/ncomms3823

[29]

Lin Q, Deng D, Song X, Dai B, Yang X, Luo Q, et al. Self‐assembled “Off/On” nanopomegranate for in vivo photoacoustic and fluorescence imaging: strategic arrangement of Kupffer cells in mouse hepatic lobules. ACS Nano. 2019;13(2): 1526–37. https://doi.org/10.1021/acsnano.8b07283

[30]

David BA, Rezende RM, Antunes MM, Santos MM, Freitas Lopes MA, Diniz AB, et al. Combination of mass cytometry and imaging analysis reveals origin, location, and functional repopulation of liver myeloid cells in mice. Gastroenterology. 2016;151(6): 1176–91. https://doi.org/10.1053/j.gastro.2016.08.024

[31]

Hessel‐Pras S, Braeuning A, Guenther G, Adawy A, Enge AM, Ebmeyer J, et al. The pyrrolizidine alkaloid senecionine induces CYP‐dependent destruction of sinusoidal endothelial cells and cholestasis in mice. Arch Toxicol. 2020;94(1): 219–29. https://doi.org/10.1007/s00204‐019‐02582‐8

[32]

Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, et al. Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol (Baltimore, Md: 1950). 2010;184(9): 4673–8. https://doi.org/10.4049/jimmunol.0903661

[33]

Andrews LP, Vignali KM, Szymczak‐Workman AL, Burton AR, Brunazzi EA, Ngiow SF, et al. A Cre‐driven allele‐conditioning line to interrogate CD4(+) conventional T cells. Immunity. 2021;54(10): 2209–17.e6. https://doi.org/10.1016/j.immuni.2021.08.029

[34]

Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int. 2006;26(10): 1175–86. https://doi.org/10.1111/j.1478‐3231.2006.01342.x

[35]

Zeng Z, Surewaard BG, Wong CH, Geoghegan J, Jenne C, Kubes P. CRIg functions as a macrophage pattern recognition receptor to directly bind and capture blood‐borne gram‐positive bacteria. Cell Host Microbe. 2016;20(1): 99–106. https://doi.org/10.1016/j.chom.2016.06.002

[36]

Sun D, Sun P, Li H, Zhang M, Liu G, Strickland AB, et al. Fungal dissemination is limited by liver macrophage filtration of the blood. Nat Commun. 2019;10(1): 4566. https://doi.org/10.1038/s41467‐019‐12381‐5

[37]

Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WC. Nanoparticle‐liver interactions: cellular uptake and hepatobiliary elimination. J Contr Release. 2016;240: 332–48. https://doi.org/10.1016/j.jconrel.2016.01.020

[38]

Bonnardel J, T'Jonck W, Gaublomme D, Browaeys R, Scott CL, Martens L, et al. Stellate cells, hepatocytes, and endothelial cells imprint the Kupffer cell identity on monocytes colonizing the liver macrophage Niche. Immunity. 2019;51(4): 638–54.e9. https://doi.org/10.1016/j.immuni.2019.08.017

[39]

Scott CL, T'Jonck W, Martens L, Todorov H, Sichien D, Soen B, et al. The transcription factor ZEB2 is required to maintain the tissue‐specific identities of macrophages. Immunity. 2018;49(2): 312–25.e5. https://doi.org/10.1016/j.immuni.2018.07.004

[40]

Gao B, Jeong WI, Tian Z. Liver: an organ with predominant innate immunity. Hepatology (Baltimore, Md). 2008;47(2): 729–36. https://doi.org/10.1002/hep.22034

[41]

Wang HT, Li LJ, Li YL, Li Y, Sha YQ, Wen S, et al. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics. 2021;11(5): 2149–69. https://doi.org/10.7150/thno.51369

[42]

Liew PX, Lee WY, Kubes P. iNKT cells orchestrate a switch from inflammation to resolution of sterile liver injury. Immunity. 2017;47(4): 752–65.e5. https://doi.org/10.1016/j.immuni.2017.09.016

[43]

Wong CH, Jenne CN, Lee WY, Leger C, Kubes P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science (New York, NY). 2011;334(6052): 101–5. https://doi.org/10.1126/science.1210301

[44]

Calne RY, Sells RA, Pena JR, Davis DR, Millard PR, Herbertson BM, et al. Induction of immunological tolerance by porcine liver allografts. Nature. 1969;223(5205): 472–6. https://doi.org/10.1038/223472a0

[45]

Zheng M, Tian Z. Liver‐mediated adaptive immune tolerance. Front Immunol. 2019;10: 2525. https://doi.org/10.3389/fimmu.2019.02525

[46]

Kurup SP, Butler NS, Harty JT. T cell‐mediated immunity to malaria. Nat Rev Immunol. 2019;19(7): 457–71. https://doi.org/10.1038/s41577‐019‐0158‐z

[47]

Bénéchet AP, De Simone G, Di Lucia P, Cilenti F, Barbiera G, Le Bert N, et al. Dynamics and genomic landscape of CD8(+) T cells undergoing hepatic priming. Nature. 2019;574(7777): 200–5. https://doi.org/10.1038/s41586‐019‐1620‐6

[48]

Martínez‐Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res. 2015;21(22): 5047–56. https://doi.org/10.1158/1078‐0432.ccr‐15‐0685

[49]

Liu L, Dai B, Li R, Liu Z, Zhang Z. Intravital molecular imaging reveals the restrained capacity of CTLs in the killing of tumor cells in the liver. Theranostics. 2021;11(1): 194–208. https://doi.org/10.7150/thno.44979

[50]

Jaeschke H, Hasegawa T. Role of neutrophils in acute inflammatory liver injury. Liver Int. 2006;26(8): 912–9. https://doi.org/10.1111/j.1478‐3231.2006.01327.x

[51]

Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285): 104–7. https://doi.org/10.1038/nature08780

[52]

Dorward DA, Lucas CD, Chapman GB, Haslett C, Dhaliwal K, Rossi AG. The role of formylated peptides and formyl peptide receptor 1 in governing neutrophil function during acute inflammation. Am J Pathol. 2015;185(5): 1172–84. https://doi.org/10.1016/j.ajpath.2015.01.020

[53]

Honda M, Takeichi T, Hashimoto S, Yoshii D, Isono K, Hayashida S, et al. Intravital imaging of neutrophil recruitment reveals the efficacy of FPR1 blockade in hepatic ischemia‐reperfusion injury. J Immunol (Baltimore, Md: 1950). 2017;198(4): 1718–28. https://doi.org/10.4049/jimmunol.1601773

[54]

Lin QY, Hong SL, Luo QM, Zhang ZH. Advances in optical microscopic imaging for visualizing liver immunology in vivo. Prog Biochem Biophys. 2017;44(12): 1056–65. https://doi.org/10.16476/j.pibb.2017.0390

[55]

Marques PE, Oliveira AG, Chang L, Paula‐Neto HA, Menezes GB. Understanding liver immunology using intravital microscopy. J Hepatol. 2015;63(3): 733–42. https://doi.org/10.1016/j.jhep.2015.05.027

[56]

Friedman SL, Neuschwander‐Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7): 908–22. https://doi.org/10.1038/s41591‐018‐0104‐9

[57]

Younossi ZM. Non‐alcoholic fatty liver disease – a global public health perspective. J Hepatol. 2019;70(3): 531–44. https://doi.org/10.1016/j.jhep.2018.10.033

[58]

Kim E, Lee Y, Lee S, Park SB. Discovery, understanding, and bioapplication of organic fluorophore: a case study with an indolizine‐based novel fluorophore, Seoul‐Fluor. Acc Chem Res. 2015;48(3): 538–47. https://doi.org/10.1021/ar500370v

[59]

Kim E, Lee S, Park SB. A Seoul‐Fluor‐based bioprobe for lipid droplets and its application in image‐based high throughput screening. Chem Commun. 2012;48(17): 2331–3. https://doi.org/10.1039/c2cc17496k

[60]

Hwang Y, Yoon H, Choe K, Ahn J, Jung JH, Park JH, et al. In vivo cellular‐level real‐time pharmacokinetic imaging of free‐form and liposomal indocyanine green in liver. Biomed Opt Express. 2017;8(10): 4706–16. https://doi.org/10.1364/boe.8.004706

[61]

Moon J, Kong E, Lee J, Jung J, Kim E, Park SB, et al. Intravital longitudinal imaging of hepatic lipid droplet accumulation in a murine model for nonalcoholic fatty liver disease. Biomed Opt Express. 2020;11(9): 5132–46. https://doi.org/10.1364/boe.395890

[62]

Frevert U, Engelmann S, Zougbédé S, Stange J, Ng B, Matuschewski K, et al. Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol. 2005;3(6): e192. https://doi.org/10.1371/journal.pbio.0030192

[63]

Tavares J, Formaglio P, Thiberge S, Mordelet E, Van Rooijen N, Medvinsky A, et al. Role of host cell traversal by the malaria sporozoite during liver infection. J Exp Med. 2013;210(5): 905–15. https://doi.org/10.1084/jem.20121130

[64]

Naumenko V, Van S, Dastidar H, Kim DS, Kim SJ, Zeng Z, et al. Visualizing oncolytic virus‐host interactions in live mice using intravital microscopy. Mol Therapy Oncolytics. 2018;10: 14–27. https://doi.org/10.1016/j.omto.2018.06.001

[65]

Wang L, Sun Y, Song X, Wang Z, Zhang Y, Zhao Y, et al. Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1‐mediated viral RNA editing in hepatocytes. Cell Mol Immunol. 2021;18(8): 1871–82. https://doi.org/10.1038/s41423‐021‐00729‐1

[66]

Brogden KA, Guthmiller JM, Taylor CE. Human polymicrobial infections. Lancet (London, England). 2005;365(9455): 253–5. https://doi.org/10.1016/s0140‐6736(05)70155‐0

[67]

Li L, Zeng Z. Live imaging of innate and adaptive immune responses in the liver. Front Immunol. 2020;11: 564768. https://doi.org/10.3389/fimmu.2020.564768

[68]

Matsumura H, Kondo T, Ogawa K, Tamura T, Fukunaga K, Murata S, et al. Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage. Int J Oncol. 2014;45(6): 2303–10. https://doi.org/10.3892/ijo.2014.2662

[69]
Tanaka K, Toiyama Y, Okugawa Y, Okigami M, Inoue Y, Uchida K, et al. In vivo optical imaging of cancer metastasis using multiphoton microscopy: a short review. Am J Transl Res. 2014 May 15;6(3): 179–87.
[70]

Yuan Y, Li H, Pu W, Chen L, Guo D, Jiang H, et al. Cancer metabolism and tumor microenvironment: fostering each other? Sci China Life Sci. 2022;65(2):236–79. https://doi.org/10.1007/s11427‐021‐1999‐2

[71]

Dai B, Zhang R, Qi S, Liu L, Zhang X, Deng D, et al. Intravital molecular imaging reveals that ROS‐caspase‐3‐GSDME‐induced cell punching enhances humoral immunotherapy targeting intracellular tumor antigens. Theranostics. 2022;12(17):7603–23. https://doi.org/10.7150/thno.75966

[72]

Montalvao F, Garcia Z, Celli S, Breart B, Deguine J, Van Rooijen N, et al. The mechanism of anti‐CD20‐mediated B cell depletion revealed by intravital imaging. J Clin Invest. 2013;123(12):5098–103. https://doi.org/10.1172/jci70972

[73]

Arlauckas SP, Garris CS, Kohler RH, Kitaoka M, Cuccarese MF, Yang KS, et al. In vivo imaging reveals a tumor‐associated macrophage‐mediated resistance pathway in anti‐PD‐1 therapy. Sci Transl Med. 2017;9(389). https://doi.org/10.1126/scitranslmed.aal3604

[74]

Zong W, Wu R, Li M, Hu Y, Li Y, Li J, et al. Fast high‐resolution miniature two‐photon microscopy for brain imaging in freely behaving mice. Nat Methods. 2017;14(7):713–9. https://doi.org/10.1038/nmeth.4305

[75]

Wu J, Lu Z, Jiang D, Guo Y, Qiao H, Zhang Y, et al. Iterative tomography with digital adaptive optics permits hour‐long intravital observation of 3D subcellular dynamics at millisecond scale. Cell. 2021;184(12):3318–32.e17. https://doi.org/10.1016/j.cell.2021.04.029

iRADIOLOGY
Pages 61-77
Cite this article:
Yuan X, Yu X, Dai B, et al. Advances in intravital imaging of liver immunity using optical microscopy and labeling methods. iRADIOLOGY, 2023, 1(1): 61-77. https://doi.org/10.1002/ird3.7

568

Views

15

Downloads

3

Crossref

Altmetrics

Received: 06 January 2023
Accepted: 08 February 2023
Published: 21 March 2023
© 2023 The Authors. Tsinghua University Press.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Return