Macrophage podosomes go 3D

Goethem, Emeline Van; Guiet, Romain; Balor, Stéphanie; Charrière, Guillaume M.; Poincloux, Renaud; Labrousse, Arnaud; Maridonneau‐Parini, Isabelle; Cabec, Véronique Le

doi:10.1016/j.ejcb.2010.07.011

Cited by 116 publications

(152 citation statements)

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“…Our results on ECM degradation, together with the real-time studies of 3D Mf migration and the detailed dynamics of CtsB activity during protrusion formation and function, suggest that the protrusive podosomes that form during mesenchymal migration are characterized by at least two functionally different regions: the protruding tip, rich in actin and adhesive molecules, and a proteolytic posterior region (the base of the protrusion). In previous studies the tips of protrusive podosomes were regarded as the main ECM-degradation sites of the invading immune cells [16,17,57]. Conversely, the highest pericellular collagenolytic activity was observed to be at the base, which is more similar to what was observed in tumor cells in 3D, where the invading leading edge develops an adhesive anterior and a proteolytic posterior [58].…”

Section: Discussionsupporting

confidence: 55%

“…It was recently suggested that protrusive podosomes of immune cells promote cell invasion, as they have been recognized as structures that degrade ECM matrix [16,17,57]. However, the mechanism by which the interplay between protrusive podosomes and ECM degradation mediates cell migration was not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…When Mfs migrate in a 3D environment (i.e., migration through Matrigel or gelled collagen I), they develop actin-rich cell protrusions that could represent the 3D counterpart of 2D podosomes [10]. The tips of these protrusive or 3D podosomes have been characterized by increased proteolytic activity and by accumulation of classical podosome markers including vinculin, talin, cortactin, and integrins [16,17]. The podosomal proteolytic activity was attributed mainly to members of the matrix metalloproteases (MMPs), principally to MMP-2, MMP-9, and MMP-14 [18]; however, the involvement of MMPs in mesenchymal migration of Mfs remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Although, U937 cells originate from a human lymphoma, the role of cysteine cathepsins in ECM degradation by PMA-differentiated U937 Mfs was extremely comparable to that of M-CSF differentiated primary human Mfs, excluding the potential influence of the cancer-related invasive phenotype. We propose that the overall process of ECM remodeling mediated by cysteine cathepsins plays a central role in facilitating Mf progression through the dense 3D matrices that trigger the protease-dependent migration mode.It was recently suggested that protrusive podosomes of immune cells promote cell invasion, as they have been recognized as structures that degrade ECM matrix [16,17,57]. However, the mechanism by which the interplay between protrusive podosomes and ECM degradation mediates cell migration was not investigated.…”

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confidence: 99%

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Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes

et al. 2012

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IntroductionThe ability of macrophages (Mfs) to progress to specific tissues, increase matrix remodeling, and induce angiogenesis is essential for their normal physiological function [1,2]. In addition, tissue infiltration of Mfs is also involved in pathological processes such as chronic inflammation, atherosclerosis, neurodegenerative disorders, and cancer progression [3]. The presence of Mfs Correspondence: Dr. Bojana Mirković e-mail: bojana.mirkovic@ffa.uni-lj.si within tumors is generally a marker of poor prognosis since they enhance angiogenesis and metastasis [4]. Furthermore, tumorassociated Mfs are emerging as essential matrix-remodeling cells during tumor-cell invasion. They have been reported to be present at high frequency at the invasive front of the tumor, where the breakdown of extracellular matrix (ECM) occurs [5]. Therefore, there is a great need to specifically control tissue infiltration of Mfs by targeting Mf migration-related molecules [6]. * These authors contributed equally to the present work. Eur. J. Immunol. 2012. 42: 3429-3441 Mf migration has been studied extensively in two dimensions (2D) on artificial substrates; however, in vivo Mfs migrate through physiological and pathological tissue and interact with the surrounding three-dimensional (3D) ECM, including basement membrane, collagen-rich interstitial matrices, and dense tissues such as tumors. Cells of different origins and/or at different differentiation stages use distinct mechanisms of cell motility in the 3D environment. In the mesenchymal mode, cells wider than the matrix pore size degrade the matrix via proteolytic and force-based matrix remodeling, thus migrating in a "path-generating" manner, while amoeboid cells squeeze through pre-existing pores in a proteaseindependent fashion in a "path-finding" mode [7,8]. The first 3D migration studies performed on cells of the immune system suggested that these cells migrate in a protease-independent fashion [7,9]. In contrast, a recent study demonstrated that Mfs adapt their migration strategy depending on the architecture of the 3D environment. In this study, Mfs were found to use the amoeboid migration mode in fibrillar collagen I and the mesenchymal migration mode in dense substrates, such as Matrigel and gelled collagen I [10].The invasion of cancer cells is facilitated by ECM-degrading invadopodia [11]. Podosomes are structures functionally similar to the invadopodia that are found in Mfs, osteoclasts, and DCs [12,13]. During migration on 2D surfaces [14], dot or ringlike podosomes form at the ventral surface of the migrating cells where they establish direct contact with the substratum and are also involved in matrix degradation [11]. Structurally, podosomes comprise a concentrated core of F-actin and actin-regulatory proteins [14]. Surrounding the core is a ring region that contains scaffolding-, signaling-, and integrin-binding proteins, including the typical focal adhesion proteins vinculin, talin, paxillin, and FAK [15]. When Mfs migrate in a 3D environment (i.e., migra...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes

et al. 2012

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“…While we cannot exclude that chemokines present in cmMTB could be involved in the migration capacity of CD16 + C-D163 + MerTK + pSTAT3 + monocyte-macrophages, we showed that STAT3-dependent acquisition of the M2-like phenotype is essential for the enhanced motility and extracellular matrix remodeling activity in these cells. This process is accompanied by MMP1 and MMP9 activity that may contribute to lung tissue damage and TB pathogenesis, as suggested by the formation of protease-mediated tunnels in 3D matrices [47,60,61], by a study demonstrating that MMP1 is increased during Mtb infection and is responsible for lung immunopathology [62], and by other reports evidencing the role of MMP9 in the recruitment of macrophages, granuloma maturation and bacterial dissemination [44]. This is an exciting finding given that, in the zebrafish and mouse models, mycobacteria infection recruits highly motile macrophages as a tool for bacterial dissemination [44,48].…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

et al. 2015

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The human CD14 + monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16 + monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16 + CD163 + MerTK + pSTAT3 + phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16 + CD163 + MerTK + pSTAT3 + cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16 + C-D163 + MerTK + pSTAT3 + monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy.

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Unraveling the Mechanobiology of the Immune System

Kim

Shin

et al. 2019

Adv Healthcare Materials

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Cells respond and actively adapt to environmental cues in the form of mechanical stimuli. This extends to immune cells and their critical role in the maintenance of tissue homeostasis. Multiple recent studies have begun illuminating underlying mechanisms of mechanosensation in modulating immune cell phenotypes. Since the extracellular microenvironment is critical to modify cellular physiology that ultimately determines the functionality of the cell, understanding the interactions between immune cells and their microenvironment is necessary. This review focuses on mechanoregulation of immune responses mediated by macrophages, dendritic cells, and T cells, in the context of modern mechanobiology.

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Macrophage podosomes go 3D

Cited by 116 publications

References 55 publications

Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes

Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

Unraveling the Mechanobiology of the Immune System

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