scholarly journals Characterization of immune cell migration using microfabrication

2021 ◽  
Author(s):  
Doriane Vesperini ◽  
Galia Montalvo ◽  
Bin Qu ◽  
Franziska Lautenschläger
Keyword(s):  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Advantages And Disadvantages ◽  
Infected Cells ◽  
Immune Cell Migration ◽  
Underlying Mechanisms

AbstractThe immune system provides our defense against pathogens and aberrant cells, including tumorigenic and infected cells. Motility is one of the fundamental characteristics that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors, even in the absence of external treatments. These processes are termed “immune surveillance.” Migration disorders of immune cells are related to autoimmune diseases, chronic inflammation, and tumor evasion. It is therefore essential to characterize immune cell motility in different physiologically and pathologically relevant scenarios to understand the regulatory mechanisms of functionality of immune responses. This review is focused on immune cell migration, to define the underlying mechanisms and the corresponding investigative approaches. We highlight the challenges that immune cells encounter in vivo, and the microfabrication methods to mimic particular aspects of their microenvironment. We discuss the advantages and disadvantages of the proposed tools, and provide information on how to access them. Furthermore, we summarize the directional cues that regulate individual immune cell migration, and discuss the behavior of immune cells in a complex environment composed of multiple directional cues.

scholarly journals Activation of NLRP3 Inflammasome Complexes by Beta-Tricalcium Phosphate Particles and Stimulation of Immune Cell Migration in vivo

2021 ◽  
pp. 1-11
Author(s):  
Kouji Maruyama ◽  
Jin-Yan Cheng ◽  
Hidee Ishii ◽  
Yu Takahashi ◽  
Vincent Zangiacomi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tricalcium Phosphate ◽  
Nlrp3 Inflammasome ◽  
Immune Cell ◽  
Dependent Manner ◽  
Potassium Efflux ◽  
Beta Tricalcium Phosphate ◽  
Immune Cell Migration ◽  
Deficient Mice

Beta-tricalcium phosphate (β-TCP) serves as a bone substitute in clinical practice because it is resorbable, biocompatible, osteointegrative, and osteoconductive. Particles of β-TCP are also inflammatory mediators although the mechanism of this function has not been fully elucidated. Regardless, the ability of β-TCP to stimulate the immune system might be useful for immunomodulation. The present study aimed to determine the effects of β-TCP particles on NLR family pyrin domain containing 3 (NLRP3) inflammasome complexes. We found that β-TCP activates NLRP3 inflammasomes, and increases interleukin (IL)-1β production in primary cultured mouse dendritic cells (DCs) and macrophages, and human THP-1 cells in caspase-1 dependent manner. In THP-1 cells, β-TCP increased also IL-18 production, and NLRP3 inflammasome activation by β-TCP depended on phagocytosis, potassium efflux, and reactive oxygen species (ROS) generation. We also investigated the effects of β-TCP in wild-type and NLRP3-deficient mice in vivo. Immune cell migration around subcutaneously injected β-TCP particles was reduced in NLRP3-deficient mice. These findings suggest that the effects of β-TCP particles in vivo are at least partly mediated by NLRP3 inflammasome complexes.

scholarly journals Manipulating leukocyte interactions in vivo through optogenetic chemokine release

Blood ◽  
2016 ◽  
Vol 127 (23) ◽  
pp. e35-e41 ◽  
Author(s):  
Milka Sarris ◽  
Romain Olekhnovitch ◽  
Philippe Bousso
Keyword(s):  
Cell Migration ◽  
Immune Cell ◽  
Cell Communication ◽  
In Situ Studies ◽  
Key Points ◽  
Immune Cell Migration

Key Points We report a method to optogenetically control the release of soluble mediators, such as chemokines, and influence immune cell migration. This approach is applicable to a variety of secreted ligands and can facilitate dynamic, in situ studies of immune cell communication.

scholarly journals Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shaun Steele ◽  
Lauren Radlinski ◽  
Sharon Taft-Benz ◽  
Jason Brunton ◽  
Thomas H Kawula
Keyword(s):  
Immune Cell ◽  
Bacterial Pathogens ◽  
Immune Surveillance ◽  
Cell Types ◽  
Antimicrobial Activities ◽  
Host Cells ◽  
Phagocytic Cells ◽  
Microbial Infections ◽  
Infected Cells

Macrophages are myeloid-derived phagocytic cells and one of the first immune cell types to respond to microbial infections. However, a number of bacterial pathogens are resistant to the antimicrobial activities of macrophages and can grow within these cells. Macrophages have other immune surveillance roles including the acquisition of cytosolic components from multiple types of cells. We hypothesized that intracellular pathogens that can replicate within macrophages could also exploit cytosolic transfer to facilitate bacterial spread. We found that viable Francisella tularensis, as well as Salmonella enterica bacteria transferred from infected cells to uninfected macrophages along with other cytosolic material through a transient, contact dependent mechanism. Bacterial transfer occurred when the host cells exchanged plasma membrane proteins and cytosol via a trogocytosis related process leaving both donor and recipient cells intact and viable. Trogocytosis was strongly associated with infection in mice, suggesting that direct bacterial transfer occurs by this process in vivo.

scholarly journals Reprogramming Immune Cells for Enhanced Cancer Immunotherapy: Targets and Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Dong ◽  
Zhuo Wan ◽  
Xiaotong Gao ◽  
Guodong Yang ◽  
Li Liu
Keyword(s):  
Immune Cells ◽  
Causes Of Death ◽  
Immune Cell ◽  
Ex Vivo ◽  
Immune Surveillance ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
The Past ◽  
Cancer Types

Cancer is one of the leading causes of death and a major public health problem all over the world. Immunotherapy is becoming a revolutionary clinical management for various cancer types. Restoration of aberrant immune surveillance on cancers has achieved markable progress in the past years by either in vivo or ex vivo engineering of the immune cells. Here, we summarized the central roles of immune cells in tumor progression and regression, and the existing and emerging strategies for different immune cell-based immunotherapies. In addition, the current challenges and the potential solutions in translating the immunotherapies into the clinic are also discussed.

Finding a Way Out: S1P Signaling and Immune Cell Migration

2020 ◽  
Vol 38 (1) ◽  
pp. 759-784 ◽  
Author(s):  
Audrey A.L. Baeyens ◽  
Susan R. Schwab
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Clinical Trials ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Sphingosine 1 Phosphate ◽  
Immune Cell Migration

The signaling lipid sphingosine 1-phosphate (S1P) plays critical roles in an immune response. Drugs targeting S1P signaling have been remarkably successful in treatment of multiple sclerosis, and they have shown promise in clinical trials for colitis and psoriasis. One mechanism of these drugs is to block lymphocyte exit from lymph nodes, where lymphocytes are initially activated, into circulation, from which lymphocytes can reach sites of inflammation. Indeed, S1P can be considered a circulation marker, signaling to immune cells to help them find blood and lymphatic vessels, and to endothelial cells to stabilize the vasculature. That said, S1P plays pleiotropic roles in the immune response, and it will be important to build an integrated view of how S1P shapes inflammation. S1P can function so effectively because its distribution is exquisitely tightly controlled. Here we review how S1P gradients regulate immune cell exit from tissues, with particular attention to key outstanding questions in the field.

scholarly journals Cell scientist to watch – Tim Lämmermann

2021 ◽  
Vol 134 (21) ◽  
Keyword(s):  
Population Dynamics ◽  
Cell Migration ◽  
Infectious Diseases ◽  
Immune Cells ◽  
Immune Cell ◽  
Group Leader ◽  
Molecular Medicine ◽  
Max Planck ◽  
Immune Cell Migration

ABSTRACT Tim Lämmermann studied molecular medicine at the Friedrich-Alexander-University, Erlangen-Nuremberg, Germany and the Lund University, Sweden. He then joined the lab of Michael Sixt at the Max Planck Institute of Biochemistry in Martinsried, where he earned his PhD in 2009 for studying the role of integrins and cytoskeletal forces in immune cell migration. Tim then moved to the National Institute of Allergy and Infectious Diseases in Bethesda, USA for his postdoc with Ron Germain. There, he worked on the mechanisms of neutrophil swarming during infection, and received the Robert-Koch Postdoctoral Award in 2014. Since 2015, Tim has been a Group Leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, where his lab investigates the single-cell and population dynamics of immune cells. He was awarded an ERC Starting Grant in 2016.

Immune Modulator Studies in Primates: The Utility of Flow Cytometry and Immunohistochemistry in the Identification and Characterization of Immunotoxicity

2003 ◽  
Vol 31 (1_suppl) ◽  
pp. 111-118 ◽  
Author(s):  
P.B. Lappin ◽  
L.E. Black
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
Immune Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Relative Distribution ◽  
Immunomodulatory Effects ◽  
Marker Expression

Exposure to natural environmental products, biopharmaceuticals, or investigational adjuvants has the potential to negatively impact the immune system, resulting in either up- or downregulation of immune function (immunomodulation). Many current protocols for primate toxicologic testing call for the evaluation of changes in immune cell number (peripheral blood or tissue), alterations in the weights of immune system organs (lymph nodes, spleen, thymus), and/or increases in the overall incidence of infections or neoplasms; these data are relied upon to suggest altered immune function. However, these are informative only when clear differences in frequency and/or severity of effects can be distinguished across control and dosed groups. In the absence of such distinct morphologic or clinical pathologic changes, the identification of potential immunomodulatory effects can present a much greater challenge. Additional evaluations may be needed to detect altered immune system integrity; these are based on in vivo assessments in primates of cellular or humoral responsiveness. Immunomodulatory effects can be characterized by in vitro or in vivo immune function tests; these tests require prestudy planning to integrate assessments into ongoing toxicology programs. These methods also involve specialized training and equipment, particularly if the intent is to evaluate parameters in a GLP laboratory setting. In primate toxicology, the added costs required to perform a complete functional analysis of the immune system can be substantial, but may be warranted depending on the clinical development plans. Two analytical methods that are easily incorporated into the standard toxicology profile in primates are flow cytometry and immunohistochemistry. Flow cytometry (FC) is used to assess changes in the relative distribution of immune cell marker expression, and where marker expression is known to fluctuate with the state of cell activation, can also provide information on functional attributes of immune cells. Immunohistochemistry (IHC) provides a means to evaluate similar characteristics of immune cells within tissue sections. Used together, FC and IHC can aid in the identification of changes in immune system that may not be apparent by traditional testing procedures (such as H&E staining), thus aiding in the characterization of immune system alterations. This presentation focused on the utility of flow cytometry and immunohistochemistry in a standard primate toxicology evaluation, with representative examples showing the benefits of these technologies in the diagnosis of potential immunomodulatory effects.

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