In Vivo Motility Patterns Displayed by Immune Cells Under Inflammatory Conditions

The migration of immune cells plays a key role in inflammation. This is evident in the fact that inflammatory stimuli elicit a broad range of migration patterns in immune cells. Since these patterns are pivotal for initiating the immune response, their dysregulation is associated with life-threatening conditions including organ failure, chronic inflammation, autoimmunity, and cancer, amongst others. Over the last two decades, thanks to advancements in the intravital microscopy technology, it has become possible to visualize cell migration in living organisms with unprecedented resolution, helping to deconstruct hitherto unexplored aspects of the immune response associated with the dynamism of cells. However, a comprehensive classification of the main motility patterns of immune cells observed in vivo, along with their relevance to the inflammatory process, is still lacking. In this review we defined cell actions as motility patterns displayed by immune cells, which are associated with a specific role during the immune response. In this regard, we summarize the main actions performed by immune cells during intravital microscopy studies. For each of these actions, we provide a consensus name, a definition based on morphodynamic properties, and the biological contexts in which it was reported. Moreover, we provide an overview of the computational methods that were employed for the quantification, fostering an interdisciplinary approach to study the immune system from imaging data.

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Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200530222426 ◽

2020 ◽

Vol 20 (9) ◽

pp. 1523-1530

Author(s):

Murat Dabak ◽

Durrin O. Dabak ◽

Tuncay Kuloglu ◽

Ersoy Baydar ◽

Hakan Bulut ◽

...

Keyword(s):

Immune Cells ◽

Low Dose ◽

Systemic Circulation ◽

Bilateral Nephrectomy ◽

Dihydroxyvitamin D3 ◽

Hydroxyvitamin D ◽

Inflammatory Conditions ◽

Calcium Phosphorus ◽

25 Hydroxyvitamin D

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

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Circulating platelet-neutrophil complexes are important for subsequent neutrophil activation and migration

Journal of Applied Physiology ◽

10.1152/japplphysiol.01086.2009 ◽

2010 ◽

Vol 109 (3) ◽

pp. 758-767 ◽

Cited By ~ 81

Author(s):

Kristin N. Kornerup ◽

Gary P. Salmon ◽

Simon C. Pitchford ◽

Wai L. Liu ◽

Clive P. Page

Keyword(s):

Inflammatory Responses ◽

Functional Expression ◽

Neutrophil Activation ◽

Neutrophil Recruitment ◽

Current Therapy ◽

Adequate Treatment ◽

Relative Contribution ◽

Inflammatory Conditions ◽

Inflammatory Stimuli

Previous studies in our laboratory have shown that platelets are essential for the migration of eosinophils into the lungs of allergic mice, and that this is dependent on the functional expression of platelet P-selectin. We sought to investigate whether the same is true for nonallergic, acute inflammatory stimuli administered to distinct anatomic compartments. Neutrophil trafficking was induced in two models, namely zymosan-induced peritonitis and LPS-induced lung inflammation, and the platelet dependence of these responses investigated utilizing mice rendered thrombocytopenic. The relative contribution of selectins was also investigated. The results presented herein clearly show that platelet depletion (>90%) significantly inhibits neutrophil recruitment in both models. In addition, we show that P-selectin glycoprotein ligand-1, but not P-selectin, is essential for neutrophil recruitment in mice in vivo, thus suggesting the existence of different regulatory mechanisms for the recruitment of leukocyte subsets in response to allergic and nonallergic stimuli. Further studies in human blood demonstrate that low-dose prothrombotic and pro-inflammatory stimuli (CCL17 or CCL22) synergize to induce platelet and neutrophil activation, as well as the formation of platelet-neutrophil conjugates. We conclude that adhesion between platelets and neutrophils in vivo is an important event in acute inflammatory responses. Targeting this interaction may be a successful strategy for inflammatory conditions where current therapy fails to provide adequate treatment.

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In Vivo Targeting of CXCR4—New Horizons

Cancers ◽

10.3390/cancers13235920 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5920

Author(s):

Margret Schottelius ◽

Ken Herrmann ◽

Constantin Lapa

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Clinical Status ◽

Inflammatory Stimuli ◽

Imaging Probes ◽

Recent Developments ◽

Chemokine Receptor 4

Given its pre-eminent role in the context of tumor cell growth as well as metastasis, the C-X-C motif chemokine receptor 4 (CXCR4) has attracted a lot of interest in the field of nuclear oncology, and clinical evidence on the high potential of CXCR4-targeted theranostics is constantly accumulating. Additionally, since CXCR4 also represents a key player in the orchestration of inflammatory responses to inflammatory stimuli, based on its expression on a variety of pro- and anti-inflammatory immune cells (e.g., macrophages and T-cells), CXCR4-targeted inflammation imaging has recently gained considerable attention. Therefore, after briefly summarizing the current clinical status quo of CXCR4-targeted theranostics in cancer, this review primarily focuses on imaging of a broad spectrum of inflammatory diseases via the quantification of tissue infiltration with CXCR4-expressing immune cells. An up-to-date overview of the ongoing preclinical and clinical efforts to visualize inflammation and its resolution over time is provided, and the predictive value of the CXCR4-associated imaging signal for disease outcome is discussed. Since the sensitivity and specificity of CXCR4-targeted immune cell imaging greatly relies on the availability of suitable, tailored imaging probes, recent developments in the field of CXCR4-targeted imaging agents for various applications are also addressed.

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Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic melanoma

10.1101/248807 ◽

2018 ◽

Author(s):

Carlos R. Figueiredo ◽

Ricardo A. Azevedo ◽

Sasha Mousdell ◽

Pedro T. Resende-Lara ◽

Lucy Ireland ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Metastatic Melanoma ◽

Immune Cells ◽

Tumour Microenvironment ◽

Innate Immune ◽

Innate Immune Cells ◽

Adaptive Immune Cells ◽

Cancer Immunotherapies

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in metastatic melanoma. The Ig-CDR-based peptide C36L1 is able to restore macrophages and dendritic cells’ immunogenic functions and to inhibit metastatic growth in vivo. Mechanistically, we found that C36L1 interferes with the MIF-CD74 tumour-innate immune cells immunosuppressive signalling pathway and thereby restores an effective anti-tumour immune response. C36L1 directly binds to CD74 on macrophages and dendritic cells, disturbing CD74 structural dynamics and inhibiting MIF signalling through CD74. Our findings suggest that interfering with MIF-CD74 immunosuppressive signalling in macrophages and dendritic cells using peptide-based immunotherapy can restore the anti-tumour immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the anti-tumour immune response.

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The Role of Syk/CARD9-Coupled C-Type Lectin Receptors in Immunity toMycobacterium tuberculosisInfections

Clinical and Developmental Immunology ◽

10.1155/2010/567571 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Mohlopheni Jackson Marakalala ◽

Lisa M. Graham ◽

Gordon D. Brown

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Mycobacterium Tuberculosis ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Lectin Receptors ◽

Molecular Patterns

There is increasing interest in understanding the mechanisms underlying the interactions that occur betweenMycobacterium tuberculosisand host innate immune cells. These cells express pattern recognition receptors (PRRs) which recognise mycobacterial pathogen-associated molecular patterns (PAMPs) and which can influence the host immune response to the infection. Although many of the PRRs appear to be redundant in the control ofM. tuberculosisinfectionin vivo, recent discoveries have revealed a key, nonredundant, role of the Syk/CARD9 signalling pathway in antimycobacterial immunity. Here we review these discoveries, as well as recent data investigating the role of the Syk/CARD9-coupled PRRs that have been implicated in mycobacterial recognition, including Dectin-1 and Mincle.

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Macrophage Inflammatory Protein 3α Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors

Journal of Experimental Medicine ◽

10.1084/jem.192.5.705 ◽

2000 ◽

Vol 192 (5) ◽

pp. 705-718 ◽

Cited By ~ 275

Author(s):

Marie-Caroline Dieu-Nosjean ◽

Catherine Massacrier ◽

Bernhard Homey ◽

Béatrice Vanbervliet ◽

Jean-Jacques Pin ◽

...

Keyword(s):

Hematopoietic Progenitor Cell ◽

Psoriatic Skin ◽

Inflammatory Conditions ◽

Inflammatory Protein ◽

Inflammatory Stimuli ◽

Epithelial Immunity ◽

Factor Α ◽

Macrophage Inflammatory Protein

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3α plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3α was the most potent chemokine inducing the selective migration of in vitro–generated CD34+ hematopoietic progenitor cell–derived LC precursors and skin LCs in accordance with the restricted MIP-3α receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3α was mainly produced by epithelial cells, and the migration of LC precursors induced by the supernatant of activated skin keratinocytes was completely blocked with an antibody against MIP-3α. (c) In vivo, MIP-3α was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3α upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3α was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1β plus tumor necrosis factor α) or T cell signals. Results of this study suggest a major role of MIP-3α in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.

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Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells

10.1101/2021.09.27.462035 ◽

2021 ◽

Author(s):

Eden L. Sikorski ◽

Janessa Wehr ◽

Noel J. Ferraro ◽

Marcos M. Pires ◽

Damien Thévenin

Keyword(s):

Immune Response ◽

Cancer Cells ◽

Immune Cells ◽

Formyl Peptide Receptor ◽

Receptor Ligand ◽

Patient Response ◽

Peptide Receptor ◽

Formyl Peptide ◽

Tumor Homing

Current immunotherapeutics often work by directing components of the immune system to recognize biomarkers on the surface of cancer cells to generate an immune response. However, variable changes in biomarker distribution and expression can result in uneven patient response. The development of a more universal tumor-homing strategy has the potential to improve selectivity and extend therapy to cancers with decreased expression or absence of specific biomarkers. Here, we designed a bifunctional agent that exploits the inherent acidic microenvironment of most solid tumors to selectively graft the surface of cancer cells with a formyl peptide receptor ligand (FPRL). Our approach is based on the pH(Low) Insertion Peptide (pHLIP), a unique peptide that selectively targets tumors in vivo by anchoring onto cancer cells in a pHdependent manner. We establish that selectively remodeling cancer cells with a pHLIP-based FPRL activates formyl peptide receptors on recruited immune cells, potentially initiating an immune response towards tumors.

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Regulation of Immune Cells by Eicosanoid Receptors

The Scientific World JOURNAL ◽

10.1100/tsw.2007.181 ◽

2007 ◽

Vol 7 ◽

pp. 1307-1328 ◽

Cited By ~ 52

Author(s):

Nancy D. Kim ◽

Andrew D. Luster

Keyword(s):

Immune Response ◽

Immune Cells ◽

Inflammatory Responses ◽

Cell Types ◽

Lipid Mediators ◽

Specific Receptor ◽

Inflammatory Conditions ◽

Specific Effects ◽

Key Players

Eicosanoids are potent, bioactive, lipid mediators that regulate important components of the immune response, including defense against infection, ischemia, and injury, as well as instigating and perpetuating autoimmune and inflammatory conditions. Although these lipids have numerous effects on diverse cell types and organs, a greater understanding of their specific effects on key players of the immune system has been gained in recent years through the characterization of individual eicosanoid receptors, the identification and development of specific receptor agonists and inhibitors, and the generation of mice genetically deficient in various eicosanoid receptors. In this review, we will focus on the receptors for prostaglandin D2, DP1and DP2/CRTH2; the receptors for leukotriene B4, BLT1and BLT2; and the receptors for the cysteinyl leukotrienes, CysLT1and CysLT2, by examining their specific effects on leukocyte subpopulations, and how they may act in concert towards the development of immune and inflammatory responses.

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Evasion of the Cell-Mediated Immune Response by Alphaherpesviruses

Viruses ◽

10.3390/v12121354 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1354

Author(s):

Naoto Koyanagi ◽

Yasushi Kawaguchi

Keyword(s):

Immune Response ◽

Natural Killer ◽

Immune Evasion ◽

Immune Cells ◽

Target Cells ◽

Latent Infections ◽

Viral Propagation ◽

Host Immune Responses ◽

Cell Mediated Immune Response

Alphaherpesviruses cause various diseases and establish life-long latent infections in humans and animals. These viruses encode multiple viral proteins and miRNAs to evade the host immune response, including both innate and adaptive immunity. Alphaherpesviruses evolved highly advanced immune evasion strategies to be able to replicate efficiently in vivo and produce latent infections with recurrent outbreaks. This review describes the immune evasion strategies of alphaherpesviruses, especially against cytotoxic host immune responses. Considering these strategies, it is important to evaluate whether the immune evasion mechanisms in cell cultures are applicable to viral propagation and pathogenicity in vivo. This review focuses on cytotoxic T lymphocytes (CTLs), natural killer cells (NK cells), and natural killer T cells (NKT cells), which are representative immune cells that directly damage virus-infected cells. Since these immune cells recognize the ligands expressed on their target cells via specific activating and/or inhibitory receptors, alphaherpesviruses make several ligands that may be targets for immune evasion. In addition, alphaherpesviruses suppress the infiltration of CTLs by downregulating the expression of chemokines at infection sites in vivo. Elucidation of the alphaherpesvirus immune evasion mechanisms is essential for the development of new antiviral therapies and vaccines.

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The Aspergillus fumigatus toxin fumagillin suppresses the immune response of Galleria mellonella larvae by inhibiting the action of haemocytes

Microbiology ◽

10.1099/mic.0.043786-0 ◽

2011 ◽

Vol 157 (5) ◽

pp. 1481-1488 ◽

Cited By ~ 44

Author(s):

John P. Fallon ◽

Emer P. Reeves ◽

Kevin Kavanagh

Keyword(s):

Immune Response ◽

Candida Albicans ◽

Aspergillus Fumigatus ◽

Immune Cells ◽

Antimicrobial Agents ◽

Galleria Mellonella ◽

Subsequent Infection ◽

Nadph Oxidase Complex ◽

Cellular Immune

Larvae of Galleria mellonella are widely used to evaluate microbial virulence and to assess the in vivo efficacy of antimicrobial agents. The aim of this work was to examine the ability of an Aspergillus fumigatus toxin, fumagillin, to suppress the immune response of larvae. Administration of fumagillin to larvae increased their susceptibility to subsequent infection with A. fumigatus conidia (P = 0.0052). It was demonstrated that a dose of 2 µg fumagillin ml−1 reduced the ability of insect immune cells (haemocytes) to kill opsonized cells of Candida albicans (P = 0.039) and to phagocytose A. fumigatus conidia (P = 0.016). Fumagillin reduced the oxygen uptake of haemocytes and decreased the translocation of a p47 protein which is homologous to p47phox, a protein essential for the formation of a functional NADPH oxidase complex required for superoxide production. In addition, toxin-treated haemocytes showed reduced levels of degranulation as measured by the release of a protein showing reactivity to an anti-myeloperoxidase antibody (P<0.049) that was subsequently identified by liquid chromatography-MS analysis as prophenoloxidase. This work demonstrates that fumagillin suppresses the immune response of G. mellonella larvae by inhibiting the action of haemocytes and thus renders the larvae susceptible to infection. During growth of the fungus in the larvae, this toxin, along with others, may facilitate growth by suppressing the cellular immune response.

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