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Breaking the Boundaries of Static Immunology: Live Imaging of Immune Responses

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Since 2002, two-photon microscopy imaging cells in living tissues has provided support for the hypothesis that rapid lymphocyte motility, and fine-tuned cell-cell interactions are essential for immune system function. Indeed all branches of the immune response appear to rely on rapid cell motility. Innate ...

Since 2002, two-photon microscopy imaging cells in living tissues has provided support for the hypothesis that rapid lymphocyte motility, and fine-tuned cell-cell interactions are essential for immune system function. Indeed all branches of the immune response appear to rely on rapid cell motility. Innate immune cell responses to pathogens and tissue damage are often immediate and highly choreographed, as demonstrated by neutrophil motility. Cell-mediated antigen delivery, rapid antigen recognition, and tissue-targeted redistribution of effector cells drive adaptive immune responses. Cell-cell interactions and sequential movement through the thymic cortex then medulla characterize selection of the T cell repertoire. T cell selection is mirrored, conceptually by the cycling of B cells through the dark and light zones of the germinal center during clonal selection. Together, indicating that B and T cell clonal selection is driven by directed, concerted cell movement, a seemingly necessary component of functional development. Active surveillance of gut microbiota is perpetual and organized by highly specialized network of adaptive cell responses. Finally, recent research has indicated that directed cell-specific interactions initiated by highly motile regulatory cells can tip the balance of an immune response in favor of immunosuppression.

This abundant evidence for the functional role of choreographed cell movement supports a re-visioning of immune cell response networks through the integration of spatiotemporal and cell-contact dependent information exchange. The ability of dendritic, T, and B cells to effect antigen-targeted responses has made these cells ideal for the development of cell-based therapies. Therefore, a data-driven map identifying high-value niches of lymphocyte activity has tremendous potential value for the design of targeted cell-based therapies. How increasingly detailed imaging data and improved analysis methods can be used to build a multi-dimensional map of immune responses that incorporates time, location, cell-cell interactions, and functional outcome is an important challenge to address.

The evolution of two-photon microscopes for live cell imaging has led to the implementation of dual-laser systems equipped with adaptive optics and high-sensitivity photomultiplier tubes (PMTs) that are capable of reliably separating eight or more fluorescent probes. High resolution imaging of cell dynamics using lattice light-sheet microscopy will undoubtedly lead to novel discoveries at the convergence of the molecular and cellular scales. Together, these imaging systems will yield ever more complex, high-density data. How we analyze and interpret this data to develop a cohesive picture of the immune system is an important consideration for the future of immunoimaging.

This Frontiers Research Topic was developed to: (1) review the advances in the field of Immunology that are a direct result of live-cell imaging; (2) spark discussion and dissemination of ideas on the future of data analysis, approaches for deconvolution of immune cell response networks, and the interpretation of complex imaging data; and (3) discuss the use of imaging data to map interaction networks or identify critical targets for improvement of cell-based therapies.

We welcome original article submissions that review current imaging technologies, analysis methods, or our current state of knowledge regarding motility of the cells of the immune system. We would also like to welcome research articles that present new data in the field of immunoimaging, data processing, analysis methods, or network modeling.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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