scholarly journals Murine CXCL14 Is Dispensable for Dendritic Cell Function and Localization within Peripheral Tissues

2006 ◽  
Vol 27 (3) ◽  
pp. 983-992 ◽  
Author(s):  
Simone Meuter ◽  
Patrick Schaerli ◽  
Regula Stuber Roos ◽  
Oliver Brandau ◽  
Michael R. Bösl ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Physiological Function ◽  
Dendritic Cell Function ◽  
Peripheral Tissues ◽  
Significant Difference ◽  
Antigen Presenting ◽  
And Control

ABSTRACT Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14 − / −) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality.

scholarly journals Role of Type I Interferons on Filovirus Pathogenesis

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 22 ◽  
Author(s):  
Beatriz Escudero-Pérez ◽  
César Muñoz-Fontela
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Marburg Virus ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune ◽  
Antigen Presenting

Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.

Role of Nutrition Counseling and Lifestyle Modification in Managing Prediabetes

2021 ◽  
pp. 037957212110254
Author(s):  
Harleen Kaur ◽  
Neerja Singla ◽  
Rohini Jain
Keyword(s):  
Hemoglobin A1c ◽  
Lifestyle Modification ◽  
Fasting Blood Glucose ◽  
Nutrition Intervention ◽  
Control Group ◽  
Population Prevalence ◽  
Significant Difference ◽  
And Control ◽  
Experimental Group

Objective: India is the second country after China having the highest population prevalence of diabetes. Several research studies investigating diabetes have been done, but not much work has been done on prediabetes. The purpose of this study was to investigate the effect of nutrition and lifestyle modification on prediabetic females. Methods: A total of 120 prediabetic females from Ludhiana city were divided into 2 matched groups: control group (n = 60) and experimental group (n = 60). Impact of nutrition intervention for dietary and lifestyle modification (for 3 months) was assessed on the anthropometric, dietary, biochemical parameters, and diabetes risk score of the experimental group and control group (no intervention). Results: All the selected 120 subjects completed the study (experimental group = 60; control group = 60). There was significant difference in the changes between the 2 groups throughout the study. The fasting blood glucose and glycated hemoglobin A1c levels of the experimental group subjects reduced significantly ( P ≤ .01). However, no change was observed among the control group subjects. The lipid profile of the experimental group showed a significant improvement ( P ≤ .01). Conclusion: Nutrition counselling of the prediabetics regarding dietary and lifestyle modification is recommended so as to improve their metabolic control, thus preventing them from being diabetics.

scholarly journals Molecular Characterization of Dendritic Cell-Derived Exosomes

1999 ◽  
Vol 147 (3) ◽  
pp. 599-610 ◽  
Author(s):  
Clotilde Théry ◽  
Armelle Regnault ◽  
Jérôme Garin ◽  
Joseph Wolfers ◽  
Laurence Zitvogel ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Heat Shock ◽  
Immune Responses ◽  
Milk Fat ◽  
Protein Composition ◽  
Antitumor Effects ◽  
Peripheral Tissues ◽  
Peptide Mass ◽  
Dc Maturation

Exosomes are membrane vesicles secreted by hematopoietic cells upon fusion of late multivesicular endosomes with the plasma membrane. Dendritic cell (DC)-derived exosomes induce potent antitumor immune responses in mice, resulting in the regression of established tumors (Zitvogel, L., A. Regnault, A. Lozier, J. Wolfers, C. Flament, D. Tenza, P. Ricciardi-Castagnoli, G. Raposo, and S. Amigorena. 1998. Nat. Med. 4:594–600). To unravel the molecular basis of exosome-induced immune stimulation, we now analyze the regulation of their production during DC maturation and characterize extensively their protein composition by peptide mass mapping. Exosomes contain several cytosolic proteins (including annexin II, heat shock cognate protein hsc73, and heteromeric G protein Gi2α), as well as different integral or peripherally associated membrane proteins (major histocompatiblity complex class II, Mac-1 integrin, CD9, milk fat globule-EGF-factor VIII [MFG-E8]). MFG-E8, the major exosomal component, binds integrins expressed by DCs and macrophages, suggesting that it may be involved in exosome targeting to these professional antigen-presenting cells. Another exosome component is hsc73, a cytosolic heat shock protein (hsp) also present in DC endocytic compartments. hsc73 was shown to induce antitumor immune responses in vivo, and therefore could be involved in the exosome's potent antitumor effects. Finally, exosome production is downregulated upon DC maturation, indicating that in vivo, exosomes are produced by immature DCs in peripheral tissues. Thus, DC-derived exosomes accumulate a defined subset of cellular proteins reflecting their endosomal biogenesis and accounting for their biological function.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

Cell-intrinsic regulation of murine dendritic cell function and survival by prereceptor amplification of glucocorticoid

Blood ◽  
2013 ◽  
Vol 122 (19) ◽  
pp. 3288-3297 ◽  
Author(s):  
Annelise Soulier ◽  
Sandra M. Blois ◽  
Shivajanani Sivakumaran ◽  
Farnaz Fallah-Arani ◽  
Stephen Henderson ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Survival ◽  
Cell Function ◽  
Cell Populations ◽  
Dendritic Cell Function ◽  
Key Points ◽  
Intrinsic Regulation

Key Points Murine dendritic cell populations are highly proficient in amplifying local glucocorticoid concentrations. This property is critical in regulating dendritic cell survival and functions in vivo.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

scholarly journals Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 168
Author(s):  
Susanna Fiorelli ◽  
Nicola Cosentino ◽  
Benedetta Porro ◽  
Franco Fabbiocchi ◽  
Giampaolo Niccoli ◽  
...  
Keyword(s):  
Progressive Increase ◽  
Human Macrophage ◽  
Plaque Morphology ◽  
Artery Disease ◽  
Atherosclerotic Process ◽  
And Function ◽  
And Control ◽  
Macrophage Accumulation

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Cell-Penetrating Peptide-Mediated Nanovaccine Delivery

2021 ◽  
Vol 22 ◽  
Author(s):  
Jizong Jiang
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cell Penetrating Peptide ◽  
Antigen Delivery ◽  
Efficient Manner ◽  
Antigen Uptake ◽  
Cell Penetrating ◽  
The Stability ◽  
Antigen Presenting

Abstract: Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10–500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.

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