Abstract
The immune system is a complex and sophisticated biological system, spanning multiple levels of complexity, from the molecular level to that of tissue. Our current understanding of its function and complexity, of the heterogeneity of leukocytes, is a result of decades of concentrated efforts to delineate cellular markers using conventional methods of antibody screening and antigen identification. In mammalian models, this led to in-depth understanding of individual leukocyte subsets, their phenotypes, and their roles in health and disease. The field was further propelled forward by the development of single-cell (sc) RNA-seq technologies, offering an even broader and more integrated view of how cells work together to generate a particular response. Consequently, the adoption of scRNA-seq revealed the unexpected plasticity and heterogeneity of leukocyte populations and shifted several long-standing paradigms of immunology. This review article highlights the unprecedented opportunities offered by scRNA-seq technology to unveil the individual contributions of leukocyte subsets and their crosstalk in generating the overall immune responses in bony fishes. Single-cell transcriptomics allow identifying unseen relationships, and formulating novel hypotheses tailored for teleost species, without the need to rely on the limited number of fish-specific antibodies and pre-selected markers. Several recent studies on single-cell transcriptomes of fish have already identified previously unnoticed expression signatures and provided astonishing insights into the diversity of teleost leukocytes and the evolution of vertebrate immunity. Without a doubt, scRNA-seq in tandem with bioinformatics tools and state-of-the-art methods, will facilitate studying the teleost immune system by not only defining key markers, but also teaching us about lymphoid tissue organization, development/differentiation, cell-cell interactions, antigen receptor repertoires, states of health and disease, all across time and space in fishes. These advances will invite more researchers to develop the tools necessary to explore the immunology of fishes, which remain non-conventional animal models from which we have much to learn.
Highlights
In the year 1891, while admirers of classical music basked in Tchaikovsky’s Nutcracker, while Maria Skłodowská entered Sorbonne University, and while Victorinox started production of its famous Swiss army knife, Joseph Lister, the respected founder of aseptic technique in surgery, brought together the leading proponents of the conflicting concepts of cellular and humoral immunity, namely É lie Metchnikoff and Paul Ehrlich, respectively, for the Seventh International Congress of Hygiene and Demography held in London, England
In traditional mammalian models, we have a comprehensive understanding of the individual leukocyte subsets, their phenotypes and their specific roles in health and pathology, allowing targeted strategies for improving our health and combating diseases
While the mammalian-centric perspective provided invaluable insights into the diversity of leukocytes and deciphered the underlying mechanisms of their interactions resulting in protective immunity, it leaves us wondering about the forces that have driven evolution and diversification of immunity to the present day
Summary
ScRNA-seq in tandem with bioinformatics tools and state-of-the-art methods, will facilitate studying the teleost immune system by defining key markers, and teaching us about lymphoid tissue organization, development/ differentiation, cell-cell interactions, antigen receptor repertoires, states of health and disease, all across time and space in fishes. These advances will invite more researchers to develop the tools necessary to explore the immunology of fishes, which remain nonconventional animal models from which we have much to learn
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