Identification of polarized macrophage subsets in zebrafish

Nguyen-Chi, Maï; Laplace-Builhé, Béryl; Trávníčková, Jana; Luz‐Crawford, Patricia; Téjédor, Gautier; Phan, Quang Tien; Duroux-Richard, Isabelle; Levraud, Jean Pierre; Kissa, Karima; Lutfalla, Georges; Jørgensen, Christian; Djouad, Farida

doi:10.7554/elife.07288

Cited by 242 publications

(345 citation statements)

References 28 publications

(37 reference statements)

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“…Comparisons between regenerative and nonregenerative model systems could help clarify which aspects of immune system reactivity are pro-versus antireparative. However, correlations between the polarization states of reactive immune cells during injury and repair in regenerative model systems have begun to be explored only recently (29).…”

Section: Significancementioning

confidence: 99%

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

White¹,

Sengupta²,

Saxena³

et al. 2017

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

152

218

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Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions. retina | microglia | glucocorticoid | regeneration | macrophage N eurodegenerative diseases are caused by the loss of discrete neuronal cell types. The goal of regenerative medicine is to reverse this process. One strategy for doing so involves harnessing the regenerative potential of endogenous neural stem cells. Unfortunately, although adult neural stem cells exist in the mammalian CNS, innate potentials for neuronal repair remain dormant in the absence of exogenous stimulation. Conversely, many other species are endowed with remarkable capacities for neuronal regeneration. For instance, in the zebrafish eye, retinal Müller glia (MG) cells can dedifferentiate to a stem cell-like state and give rise to progenitors that replace lost neurons and restore visual function (1, 2). Intriguingly, human MG cells are able to give rise to new neurons in culture (3) that can restore visual function when transplanted into mammalian disease models (4), suggesting that human MG retain a stem cell-like capacity for mediating retinal repair. Mechanisms controlling the regenerative potential of MG are therefore of great interest. We and others study zebrafish to learn more about how retinal regeneration is cont...

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Section: Significancementioning

confidence: 99%

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

White¹,

Sengupta²,

Saxena³

et al. 2017

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

152

218

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“…Cell sorted tnfa + and tnfa -polarized macrophages activated during the regeneration process, respectively expressed some mammalian markers of M1 and M2 macrophages. During the time-course of inflammation, pro-inflammatory macrophages converted into M2-like phenotype [51] . Live imaging of zebrafish larvae permitted the first real time visualization of macrophage activation and polarization demonstrating the diversity and plasticity of zebrafish macrophage subsets.…”

Section: Macrophage Polarization In Zebrafishmentioning

confidence: 99%

“…This controversy underlined the need for accurate real-time tracing of macrophage sub-populations in vivo in response to various environmental cues. The existence of macrophage subtypes in zebrafish has been recently addressed using transgenic reporter zebrafish lines reporting the activated states of macrophages in response to stress [50,51] . Immunoresponsive gene 1 (irg1) encodes a mitochondria-localizing enzyme that is involved in bactericidal activity of Macrophages.…”

Section: Macrophage Polarization In Zebrafishmentioning

confidence: 99%

“…This line allowed us to track activated macrophages during the multi-step inflammation process induce by wounding and during infection. Injection in the muscle of live E. coli expressing E2-crimson fluorescent protein leads to the recruitment of macrophages and their subsequent activation while engulfing fluorescent bacteria [51] . We showed that caudal fin amputation-mediated inflammation triggered macrophage recruitment, some of which started to adopt a M1-like phenotype expressing tnfa.…”

Section: Macrophage Polarization In Zebrafishmentioning

confidence: 99%

“…Therefore, innovative strategies which seek to deplete macrophages or modulate their functions could be developed in order to alter the outcome of the diseases. [33,51] mpeg1: GAL4 macrophage express 1 promoter, macrophage reporter line [36] mpeg1: kaede macrophage express 1 promoter, macrophage reporter line with photoconvertible fluorescent protein [35] csf1r:GAL4 macrophage colony stimulating factor (fms) reporter line which marks both macrophages and xanthophores [53] mfap4:tdTomato microfibrillar-associated protein 4 promoter, macrophage reporter line [54] Transgenic reporter lines to visualize macrophage subsets and activation irg1:EGFP immunoresponsive gene 1 reporter line, which marks activated macrophages [50] tnfa: GFP-F tumor necrosis factor a reporter line, which marks M1-Like polarized macrophages [51] Transgenic lines to ablate macrophage mpeg1:GAL4/ UAS:nfsb-mCherry Escherichia coli enzyme nitroreductase expression in macrophage, inducible ablation of macrophages [55] mpeg1:nfsb-eYFP Escherichia coli enzyme nitroreductase expression in macrophage, inducible ablation of macrophages [47] csf1r:GAL4 / UAS:nfsb-mCherry Escherichia coli enzyme nitroreductase expression in macrophage, inducible ablation of macrophages [53,56] Other methods for macrophage ablation MO PU. 1 Decrease of macrophage number with increase of neutrophil number [36,60] …”

Section: Introductionmentioning

confidence: 99%

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Deciphering the complexity of macrophage biology and function with the zebrafish model

Nguyen-Chi¹,

Laplace-Builhé²,

Jorgensen³

et al. 2016

Macrophage

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Macrophages are present in every tissue of the body. Acting as sentinels of the immune system, they have the ability to engulf apoptotic cells and pathogens and also produce effector signals to mount a proper immune response. In response to tissue injury or microbe invasion, they are rapidly recruited to the injured site and are main key players in the protection of the host. Associated with many diseases, macrophages can have deleterious roles, especially due to their pro-inflammatory function. However, macrophages were discovered to be central during the orchestration of every step of inflammation, from initiation to resolution phases and to participate in tissue development, homeostasis and repair. These plural functions exerted by macrophages support their high plasticity and versatility potential and suggest the existence of macrophage subsets that might be differentially activated and/or recruited during physiological and pathological processes. The study of macrophage behaviour dynamics and functions in their activated states requires tractable in vivo models in which macrophages can be visualized under physiological or stress conditions. Thus, the zebrafish (Danio rerio) has emerged as an excellent vertebrate system to study myeloid development, inflammation and host-pathogen interactions. Conservation of immune cell lineage, optical accessibility of the zebrafish embryo combined with genetic approaches unable us to improve our understanding of macrophage functions. In this review, we discuss recent studies that have used the zebrafish advantages to provide key advances in the field of vertebrate macrophage biology and functions.

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Gradual specialization of phagocytic ameboid cells may have impaired regenerative capacities in metazoan lineages

Lima

Abrahão

Pentagna

et al. 2022

Developmental Dynamics

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Animal regeneration is a fascinating field of research that has captured the attention of many generations of scientists. Among the cellular mechanisms underlying tissue and organ regeneration, we highlight the role of phagocytic ameboid cells (PACs). Beyond their ability to engulf nutritional particles, microbes, and apoptotic cells, their involvement in regeneration has been widely documented. It has been extensively described that, at least in part, animal regenerative mechanisms rely on PACs that serve as a hub for a range of critical physiological functions, both in health and disease. Considering the phylogenetics of PAC evolution, and the loss and gain of nutritional, immunological, and regenerative potential across Metazoa, we aim to discuss when and how phagocytic activity was first co‐opted to regenerative tissue repair. We propose that the gradual specialization of PACs during metazoan derivation may have contributed to the loss of regenerative potential in animals, with critical impacts on potential translational strategies for regenerative medicine.

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Identification of polarized macrophage subsets in zebrafish

Cited by 242 publications

References 28 publications

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

Deciphering the complexity of macrophage biology and function with the zebrafish model

Gradual specialization of phagocytic ameboid cells may have impaired regenerative capacities in metazoan lineages

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