Myeloid Growth Factors Promote Resistance to Mycobacterial Infection by Curtailing Granuloma Necrosis through Macrophage Replenishment

Pagán, Antonio J.; Yang, Chao-Tsung; Cameron, James; Swaim, Laura E.; Ellett, Felix; Lieschke, Graham J.; Ramakrishnan, Lalita

doi:10.1016/j.chom.2015.06.008

Cited by 101 publications

(120 citation statements)

References 64 publications

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“…At 3 dpf clodronate‐filled liposomes, (1:1 [v/v] diluted in phenol red, 10 nl end volume) were injected into the caudal vein, to deplete the larvae of all residual systemic phagocytes (Bernut et al, 2014; Pagán et al, 2015; Van Rooijen & Sanders, 1994). …”

Section: Methodsmentioning

confidence: 99%

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Leeuwen

Boot

Kuijl

et al. 2018

Cellular Microbiology

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Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialised barriers protecting the brain. How M. tuberculosis crosses the blood–brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development, mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages. After the formation of a functionally intact BBB, the infiltration of brain tissue by infected macrophages is delayed, but not blocked, suggesting that crossing the BBB via phagocytic cells is one of the mechanisms used by mycobacteria to invade the CNS. Interestingly, depletion of phagocytic cells did not prevent M. marinum from infecting the brain tissue, indicating that free mycobacteria can independently cause brain infection. Detailed analysis showed that mycobacteria are able to cause vasculitis by extracellular outgrowth in the smaller blood vessels and by infecting endothelial cells. Importantly, we could show that this second mechanism is an active process that depends on an intact ESX‐1 secretion system, which extends the role of ESX‐1 secretion beyond the macrophage infection cycle.

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Section: Methodsmentioning

confidence: 99%

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Leeuwen

Boot

Kuijl

et al. 2018

Cellular Microbiology

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“…The majority of the procedures applied and all transgenic lines used, Tg(rho: YFP-Eco.NfsB)gmc500, Tg(mpx:GFP)uwm1, Tg(mpeg1.1:LOX2272-LOXP-dTomato-LOX2272-Cerulean-LOXP-EYFP)w201, Tg(mpeg1.1:NTR-EYFP)w202, and Tg(gfap: GFP)m2001, have been previously published (8,20,22,39,41,47). Brief descriptions of the experimental design are outlined here; additional details can be found in SI Materials and Methods and references provided.…”

Section: Methodsmentioning

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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“…Inversely, increasing macrophage supply to the granuloma delays the process of granuloma necrosis. Therefore, this study reveals that macrophage supply boost with myeloid growth factors might be a host-targeting therapy for TB [19] . Interestingly, a recent work on Mycobacterium abscessus (M. abscessus) infection in zebrafish larvae have shown a role of macrophages in the transport of the bacteria to the central nervous system (CNS) [33] .…”

Section: Role Of Macrophages In Host-pathogen Interactions In Zebrafishmentioning

confidence: 99%

“…The importance of macrophage supply and demand in granuloma fate was recently highlighted using M. marinum infected embryo system [19] . Indeed, during the first phase of granuloma growth, a macrophage demand leads to the recruitment of new macrophages.…”

Section: Role Of Macrophages In Host-pathogen Interactions In Zebrafishmentioning

confidence: 99%

“…Primitive macrophages then invade the embryo (the mesenchyme of the head, blood circulation, etc). The migration of primitive macrophages in the embryonic tissues and subsequent microglia formation in the head require the expression of M-CSF receptor/fms/csf1r gene [18,19] . Then, from 26 to 48 hpf, a transient wave of definitive hematopoiesis takes place in blood islands with the specification of multipotent erythro-myeloid progenitors.…”

Section: Macrophage Ontogeny In Zebrafishmentioning

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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Myeloid Growth Factors Promote Resistance to Mycobacterial Infection by Curtailing Granuloma Necrosis through Macrophage Replenishment

Cited by 101 publications

References 64 publications

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

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

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