In Vivo Optical Imaging for Immune Response

Abstract

Cells of the immune system play a critical role in defence against invading microorganisms. Conventional histological analysis can provide protein expression level better than cell morphology and location. In contrast, intravital imaging shows a great potential in monitoring the dynamic process of the immune response, from cell–cell interactions to cell–molecule interactions. In particular, in vivo optical imaging can track the dynamics of the immune response with high spatiotemporal resolution. This article introduces the development of in vivo optical imaging for immune responses in various tissues and organs, using different imaging windows.

Key Concepts

  • Immune response is a physiological process of the immune system against antigen stimulation. It is a complicated dynamic response including activation of immune cells and the effect of immune‐mediated factors.
  • Intravital multiphoton imaging has the advantages of lower photobleaching and phototoxicity, deeper imaging depth and subcellular resolution, which is a significant tool for visualisation of cell–cell and cell–molecule interactions under pathophysiologic conditions.
  • Microglia, as a sentinel, participate in the immune response of the brain, whose immune behaviour plays an important role in the brain function and brain diseases.
  • Skin has essential immunological functions as the first line of defence against foreign antigen challenges, which is an ideal organ to study the immune response due to its accessibility.
  • Tissue optical clearing methods can effectively improve optical imaging resolution and depth, which have shown a great potential in immunology research.

Keywords: immune response; intravital optical imaging; noninvasive; spatiotemporal resolution; tissue optical clearing

Figure 1. The skin imaging windows for the study of intravital optical immunoimaging. (a) Zinselmeyer et al. . Reproduced with permission of Springer Nature. (b) Goh et al. . Reproduced with permission of My JoVE corporation.
Figure 2. Intravital imaging of microglia immune response under different conditions. (a) Microglia motility in resting state. Baik et al. . Reproduced with permission of Wiley. (b) Microglia response induced by laser ablation. Davalos et al. . Reproduced with permission of Springer Nature. (c) Microglia response with amyloid β plaque. Baik et al. . Reproduced with permission of Wiley.
Figure 3. Intravital imaging immune response of various tissues and organs. (a) Intravital lymph node imaging for monitoring the growth of cancer cells. Meijer et al. . Reproduced with permission of Springer Nature. (b) Intravital imaging of T‐cell transfer in tumour. Schietinger et al. . Reproduced with permission of Taylor & Francis Ltd.
Figure 4. The in vivo optical clearing footpad skin imaging windows for improvement of intravital optical imaging. (a) In vivo footpad skin optical clearing method for improvement of imaging contrast and depth. Shi et al. . Reproduced with permission of Wiley‐VCH Verlag GmbH & Co. KGaA. (b) Visualisation of imaging MMs at different skin depths. Shi et al. and Tainaka et al. . Reproduced with permission of Wiley‐VCH Verlag GmbH & Co. KGaA.
close

References

Alieva M, Ritsma L, Giedt RJ, Weissleder R and van Rheenen J (2014) Imaging windows for long‐term intravital imaging: general overview and technical insights. Intravital 3 (2): e29917.

Amornphimoltham P, Masedunskas A and Weigert R (2011) Intravital microscopy as a tool to study drug delivery in preclinical studies. Advanced Drug Delivery Reviews 63 (1–2): 119–128.

Ankeny DP, Guan Z and Popovich PG (2009) B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice. Journal of Clinical Investigation 119 (10): 2990–2999.

Antonios JP, Soto H, Everson RG, et al. (2017) Detection of immune responses after immunotherapy in glioblastoma using PET and MRI. Proceedings of the National Academy of Sciences of the United States of America 114 (38): 10220–10225.

Arcuri C, Mecca C, Bianchi R, Giambanco I and Donato R (2017) The pathophysiological role of microglia in dynamic surveillance, phagocytosis and structural remodeling of the developing CNS. Frontiers in Molecular Neuroscience 10: 191–212.

Auffray C, Fogg D, Garfa M, et al. (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317 (5838): 666–670.

Baik SH, Kang S, Son SM and Mook‐Jung I (2016) Microglia contributes to plaque growth by cell death due to uptake of amyloid beta in the brain of Alzheimer's disease mouse model. Glia 64 (12): 2274–2290.

Beckford Vera DR, Smith CC, Bixby LM, et al. (2018) Immuno‐PET imaging of tumor‐infiltrating lymphocytes using zirconium‐89 radiolabeled anti‐CD3 antibody in immune‐competent mice bearing syngeneic tumors. PLoS ONE 13 (3): e0193832.

Belkaid Y and Tamoutounour S (2016) The influence of skin microorganisms on cutaneous immunity. Nature Reviews Immunology 16 (6): 353–366.

Cerami C, Iaccarino L and Perani D (2017) Molecular imaging of neuroinflammation in neurodegenerative dementias: the role of in vivo PET imaging. International Journal of Molecular Sciences 18 (5): 993.

Davalos D, Grutzendler J, Yang G, et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8 (6): 752–758.

Debasish S, Luette F, Thomas BK, Ian P and Michael DC (2010) Selective and site‐specific mobilization of dermal dendritic cells and Langerhans cells by Th1‐ and Th2‐polarizing adjuvants. Proceedings of the National Academy of Sciences of the United States of America 107 (18): 8334–8339.

Dorand RD, Barkauskas DS, Evans TA, Petrosiute A and Huang AY (2014) Comparison of intravital thinned skull and cranial window approaches to study CNS immunobiology in the mouse cortex. Intravital 3 (2): e29728.

Efthymiou AG and Goate AM (2017) Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk. Molecular Neurodegeneration 12 (1): 43.

Fenrich KK, Weber P, Hocine M, et al. (2012) Long‐term in vivo imaging of normal and pathological mouse spinal cord with subcellular resolution using implanted glass windows. Journal of Physiology 590 (16): 3665.

Garnett MJ, Edelman EJ, Heidorn SJ, et al. (2012) Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483 (7391): 570–575.

Gibson VB, Benson RA, Bryson KJ, et al. (2012) A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo. Blood 119 (11): 2545–2551.

Gligorijevic B, Kedrin D, Segall JE, Condeelis J and van Rheenen J (2009) Dendra2 photoswitching through the Mammary Imaging Window. Journal of Visualized Experiments 28: e1278.

Goh CC, Li JL, Becker D, et al. (2016) Inducing ischemia‐reperfusion injury in the mouse Ear skin for intravital multiphoton imaging of immune responses. Journal of Visualized Experiments 118: e54956.

Goldmann T, Wieghofer P, Jordao MJ, et al. (2016) Origin, fate and dynamics of macrophages at central nervous system interfaces. Nature Immunology 17 (7): 797–805.

Gomez‐Nicola D, Fransen NL, Suzzi S and Perry VH (2013) Regulation of microglial proliferation during chronic neurodegeneration. Journal of Neuroscience 33 (6): 2481–2493.

Graf BW, Chaney EJ, Marjanovic M, et al. (2013) In vivo imaging of immune cell dynamics in skin in response to zinc‐oxide nanoparticle exposure. Biomedical Optics Express 4 (10): 1817–1828.

Honda T, Otsuka A and Kabashima K (2016) Novel insights into cutaneous immune systems revealed by in vivo imaging. Allergology International 65 (3): 228–234.

Honda T and Kabashima K (2017) In vivo imaging of cutaneous inflammation: novel insights into cutaneous immune responses revealed by multi‐photon microscopic analysis. The Japan Society for Clinical Immunology 40 (5): 337–343.

Ipponjima S, Hibi T and Nemoto T (2016) Three‐dimensional analysis of cell division orientation in epidermal basal layer using intravital two‐photon microscopy. PLoS ONE 11 (9): e0163199.

Ishii M (2016) Intravital imaging technology reveals immune system dynamics in vivo. Allergology International 65 (3): 225–227.

Herz J, Paterka M, Niesner RA, et al. (2011) In vivo imaging of lymphocytes in the CNS reveals different behaviour of naive T cells in health and autoimmunity. Journal of Neuroinflammation 8 (1): 131.

Kikuta J and Ishii M (2018) Bone imaging: osteoclast and osteoblast dynamics. In: Intravital Imaging of Dynamic Bone and Immune Systems, pp. 1–9. New York: Humana Press.

Li H, Qi S, Jin H, et al. (2015) Zigzag generalized levy walk: the in vivo search strategy of immunocytes. Theranostics 5 (11): 1275–1290.

Liu Z, Yang F, Zheng H, et al. (2018) Visualization of T cell‐regulated monocyte clusters mediating keratinocyte death in acquired cutaneous immunity. Journal of Investigative Dermatology 138 (6): 1328–1337.

Looney MR, Thornton EE, Sen D, et al. (2011) Stabilized imaging of immune surveillance in the mouse lung. Nature Methods 8 (1): 91–96.

Luo M, Zhang Z, Li H, et al. (2014) Multi‐scale optical imaging of the delayed type hypersensitivity reaction attenuated by rapamycin. Theranostics 4 (2): 201–214.

Matheu MP, Othy S, Greenberg ML, et al. (2015) Imaging regulatory T cell dynamics and CTLA4‐mediated suppression of T cell priming. Nature Communications 6: 6219.

Meijer EFJ, Jeong HS, Pereira ER, et al. (2017) Murine chronic lymph node window for longitudinal intravital lymph node imaging. Nature Protocols 12 (8): 1513–1520.

Millington OR, Brewer JM, Garside P and Maffia P (2010) Imaging interactions between the immune and cardiovascular systems in vivo by multiphoton microscopy. Methods in Molecular Biology 616 (3): 193–206.

Murata T, Honda T, Egawa G, et al. (2017) Three‐dimensional evaluation of subclinical extension of extramammary Paget disease: visualization of the histological border and its comparison to the clinical border. The British Journal of Dermatology 177 (1): 229–237.

Navegantes KC, De SGR, Pereira PA, et al. (2017) Immune modulation of some autoimmune diseases: the critical role of macrophages and neutrophils in the innate and adaptive immunity. Journal of Translational Medicine 15 (1): 36.

Nimmerjahn A, Kirchhoff F and Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308 (5726): 1314–1318.

Palmer GM, Fontanella AN, Shan S, et al. (2011) In vivo optical molecular imaging and analysis in mice using dorsal window chamber models applied to hypoxia, vasculature and fluorescent reporters. Nature Protocols 6 (9): 1355–1366.

Prinz M and Priller J (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nature Reviews Neuroscience 15 (5): 300–312.

Ritsma L, Steller EJA, Ellenbroek SIJ, et al. (2013) Surgical implantation of an abdominal imaging window for intravital microscopy. Nature Protocols 8 (3): 583–594.

Ritsma L, Ellenbroek SIJ, Zomer A, et al. (2014) Intestinal crypt homeostasis revealed at single‐stem‐cell level by in vivo live imaging. Nature 507 (7492): 362–365.

Rodero MP, Licata F, Poupel L, et al. (2014) In vivo imaging reveals a pioneer wave of monocyte recruitment into mouse skin wounds. PLoS ONE 9 (10): e108212.

Salter MW and Stevens B (2017) Microglia emerge as central players in brain disease. Nature Medicine 23 (9): 1018–1027.

Schietinger A, Arina A, Liu RB, et al. (2013) Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer. Oncoimmunology 2 (11): e26677.

Schwarzmaier SM and Plesnila N (2014) Contributions of the immune system to the pathophysiology of traumatic brain injury ‐ evidence by intravital microscopy. Frontiers in Cellular Neuroscience 8: 358.

Shi R, Feng W, Zhang C, et al. (2017a) In vivo imaging the motility of monocyte/macrophage during inflammation in diabetic mice. Journal of Biophotonics 11: e201700205.

Shi R, Feng W, Zhang C, Zhang Z and Zhu D (2017b) FSOCA‐induced switchable footpad skin optical clearing window for blood flow and cell imaging in vivo. Journal of Biophotonics 10 (12): 1647–1656.

Tainaka K, Kuno A, Kubota SI, Murakami T and Ueda HR (2016) Chemical principles in tissue clearing and staining protocols for whole‐body cell profiling. Annual Review of Cell and Developmental Biology 32 (1): 713–741.

Tanabe S and Yamashita T (2018) The role of immune cells in brain development and neurodevelopmental diseases. International Immunology 30 (10): 437–444.

Thiel A and Heiss WD (2011) Imaging of microglia activation in stroke. Stroke 42 (2): 507–512.

Vakoc BJ, Lanning RM, Tyrrell JA, et al. (2009) Three‐dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nature Medicine 15 (10): 1219–1223.

van de Ven AL, Kim P, Ferrari M and Yun SH (2013) Real‐time intravital microscopy of individual nanoparticle dynamics in liver and tumors of live mice. Protocol Exchange 2013.

Wang J, Shi R, Zhang Y and Zhu D (2013) Ear skin optical clearing for improving blood flow imaging/Optisches Clearing der Ohrhaut zur verbesserten Bildgebung des Blutflusses. Photonics and Lasers in Medicine 2 (1): 37–44.

Wang XN, McGovern N, Gunawan M, et al. (2014) A three‐dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels. Journal of Investigative Dermatology 134 (4): 965–974.

Wyckoff JB, Wang Y, Lin EY, et al. (2007) Direct visualization of macrophage‐assisted tumor cell intravasation in mammary tumors. Cancer Research 67 (6): 2649–2656.

Yang F, Qi SH, Luo QM and Zhang ZH (2017) In vivo optical imaging of anti‐tumor immune response. In: International Conference on Photonics and Imaging in Biology and Medicine, p. T1B.3. USA: Optical Society of America.

Yu T, Qi Y, Gong H, Luo Q and Zhu D (2018) Optical clearing for multiscale biological tissues. Journal of Biophotonics 11 (2): e201700187.

Zeng Y, Yan B, Xu J, et al. (2014) In Vivo nonlinear optical imaging of immune responses: tissue injury and infection. Biophysical Journal 107 (10): 2436–2443.

Zhang C, Feng W, Zhao Y, et al. (2018) A large, switchable optical clearing skull window for cerebrovascular imaging. Theranostics 8 (10): 2696–2708.

Zhao Y, Yu T, Zhang C, et al. (2018) Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution. Light: Science & Applications 7 (2): 17153.

Zhu D, Wang J, Zhi Z, Wen X and Luo Q (2010) Imaging dermal blood flow through the intact rat skin with an optical clearing method. Journal of Biomedical Optics 15 (2): 026008.

Zhu D, Larin KV, Luo QM and Tuchin VV (2013) Recent progress in tissue optical clearing. Laser & Photonics Reviews 7 (5): 732–757.

Zinselmeyer BH, Lynch JN, Zhang X, Aoshi T and Miller MJ (2008) Video‐rate two‐photon imaging of mouse footpad ‐ a promising model for studying leukocyte recruitment dynamics during inflammation. Inflammation Research 57 (3): 93–96.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Liu, Shaojun, Feng, Wei, Zhang, Chao, Yu, Tingting, and Zhu, Dan(Apr 2019) In Vivo Optical Imaging for Immune Response. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027292]