Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue

Qi, Hai; Kastenmüller, Wolfgang; Germain, Ronald N.

doi:10.1146/annurev-cellbio-100913-013254

Cited by 156 publications

(124 citation statements)

References 177 publications

(213 reference statements)

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“…4C). Importantly, XYZ positioning for all gated cell populations precisely mirrored the original image dataset and the expected physiological compartmentalization (23,24), suggesting accurate cellular segmentation, analysis, and spatial allocation ( Fig. 4D and Movie S6).…”

Section: Resultsmentioning

confidence: 71%

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Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)

Germain

Gerner

2017

Proc. Natl. Acad. Sci. U.S.A.

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237

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Organ homeostasis, cellular differentiation, signal relay, and in situ function all depend on the spatial organization of cells in complex tissues. For this reason, comprehensive, high-resolution mapping of cell positioning, phenotypic identity, and functional state in the context of macroscale tissue structure is critical to a deeper understanding of diverse biological processes. Here we report an easy to use method, clearing-enhanced 3D (C e 3D), which generates excellent tissue transparency for most organs, preserves cellular morphology and protein fluorescence, and is robustly compatible with antibody-based immunolabeling. This enhanced signal quality and capacity for extensive probe multiplexing permits quantitative analysis of distinct, highly intermixed cell populations in intact C e 3D-treated tissues via 3D histo-cytometry. We use this technology to demonstrate large-volume, high-resolution microscopy of diverse cell types in lymphoid and nonlymphoid organs, as well as to perform quantitative analysis of the composition and tissue distribution of multiple cell populations in lymphoid tissues. Combined with histo-cytometry, C e 3D provides a comprehensive strategy for volumetric quantitative imaging and analysis that bridges the gap between conventional section imaging and disassociation-based techniques.tissue clearing | quantitative microscopy | histo-cytometry | immune system M ajor physiological processes rely on the precise positioning of diverse cell types in specific anatomical locations. Such organization allows exposure of cells to appropriate tissue microenvironments that shape their differentiation, promote appropriate cell-cell communication events, and collectively define the global properties of the whole organ. Understanding these structure-function relationships requires a detailed mapping of both the large-scale organization and fine-grained molecular and cellular composition of complex tissues.The majority of information on such processes comes from microscopic imaging of relatively thin (5-20 μm) "2D" tissue crosssections, examining several markers of interest to visualize a limited number of cell populations with respect to a tissue's representative structural elements. Although providing an excellent framework for understanding general features and the respective positioning of well-represented cell types, such data lack information on 3D organization, being particularly limiting for irregular structures such as the vasculature, airways, nervous tissue, inflamed sites, tumors, or reactive lymph nodes. Furthermore, detection and analysis of rare cellular events requires imaging of a large number of disconnected sections, which introduces possible image selection bias and suffers from the potential omission of key physiological landmarks located just outside of the sampled area. Finally, many cell types require simultaneous visualization of multiple phenotypic markers for correct subset identification, making interpretation of cell composition within tissues problematic without the use...

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Section: Resultsmentioning

confidence: 71%

“…3B). Importantly, analysis of the cellular position of the gated cell types revealed physiologically appropriate localization in LN tissues (23,24), with positioning of B cells in the peripheral follicular regions and with T cells concentrated in the central T-cell zone (Fig. 3C).…”

Section: Resultsmentioning

confidence: 98%

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)

Germain

Gerner

2017

Proc. Natl. Acad. Sci. U.S.A.

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237

265

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“…Defence of the host organism against an infectious challenge is a primary function of the immune system associated with generation of potent responses [1]. Understanding the processes and parameters that underline fate decision between resolving and chronic dynamics of the virus infections such as CMV, HBV, HCV, HIV is a challenge.…”

Section: Introductionmentioning

confidence: 99%

Modelling the dynamics of virus infection and immune response in space and time

Bocharov

Meyerhans

Bessonov

et al. 2017

International Journal of Parallel, Emergent and Distributed Sys

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International audienceSpreading of viral infection in the tissues such as lymph nodes or spleendepends on virus multiplication in the host cells, their transport andon the immune response. Reaction–diffusion systems of equations withdelays in proliferation and death terms of the immune cells represent anappropriate model to study this process. The properties of the immuneresponse and the initial viral load determine the regimes of infectionspreading. In the proposed model, the proliferation rate of the immunecells is represented by a bell-shaped function of the virus concentrationwhich increases for small concentrations and decreases if the concentrationis sufficiently high. Here we use such a model system to show that aninfection can be completely eliminated or it can remain present togetherwith a decreased concentration of immune cells. Finally, immune cellscan be completely exhausted leading to a high virus concentration in thetissue. In addition, we predicted two novel regimes of infection dynamicsnot observed before. Infection propagation in the tissue can occur asa superposition of two travelling waves: first wave propagates as a lowlevel infection front followed by a high level infection front with a smallerspeed of propagation. Both of the travelling waves can have a positive or anegative speed corresponding to infection advancement or retreat. Theseregimes can be accompanied by instabilities and the emergence of complexspatiotemporal patterns

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“…The anatomical and molecular cues direct the cell and uid movements to ensure that the antigens can meet the right immune cells e ectively 1,2 . Advanced 3D imaging techinques 1 allowed the scientists to visualize the lymph nodes.…”

mentioning

confidence: 99%

Lymphatic Voyage: Communicating 4D Immune Cell Dynamics and Lymph Node Architecture using WebGL-based Animation and Interactivity

Li¹,

Gregg²,

Germain³

et al. 2018

JBC

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Lymph nodes are secondary lymphoid organs where Tcells and B cells meet antigens to initiate adaptiveimmune responses. The anatomical and molecular cuesdirect the cell and uid movements to ensure that theantigens can meet the right immune cells eectively1,2.Advanced 3D imaging techinques1 allowed the scientiststo visualize the lymph nodes. However, Teaching lymphnode architecture and immune cell dynamics at thecellular level is challenging due to the lack of visualteaching tools. Lymphatic Voyage is a widely accessibleitneractive 3D app designed as an educational tool tohelp instructors and graduate students.

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Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue

Cited by 156 publications

References 177 publications

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)

Modelling the dynamics of virus infection and immune response in space and time

Lymphatic Voyage: Communicating 4D Immune Cell Dynamics and Lymph Node Architecture using WebGL-based Animation and Interactivity

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Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue

Cited by 156 publications

References 177 publications

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C e 3D)

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C e 3D)

Modelling the dynamics of virus infection and immune response in space and time

Lymphatic Voyage: Communicating 4D Immune Cell Dynamics and Lymph Node Architecture using WebGL-based Animation and Interactivity

Contact Info

Product

Resources

About

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (C _e 3D)