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Journal of Leukocyte Biology

Aparna Mahajan, Anika Grüneboom, Lenka Petru, Malgorzata J Podolska, Lasse Kling, Christian Maueröder, Florian Dahms, Silke Christiansen, Lochnit Günter, Veit Krenn, Anselm Jünemann, Felix Bock, Christine Schauer, Georg Schett, Bettina Hohberger, Martin Herrmann, Luis E Muñoz
Eye rheum is a physiological discharge, which accumulates at the medial angle of the healthy eye soon after opening in the morning. Microscopic evaluation of eye rheum revealed the presence of viable neutrophils, bacteria, epithelial cells, and particles, aggregated by neutrophil extracellular traps. We observed that in the evening, during eye closure, high C5a recruited neutrophils to the tear film and activated them. In this hypoxic area rich in CO2 , neutrophils fight microbial aggressors by degranulation...
April 12, 2019: Journal of Leukocyte Biology
Kayla A Holder, Michael D Grant
Human cytomegalovirus (HCMV) persistently infects most of the adult population with periods of productive and latent infection differentially orchestrated by multiple HCMV-encoded gene products. One HCMV gene (UL111a) encodes cmvIL-10, a virokine homologous to human IL (hIL)-10. Although the effects of cmvIL-10 on most human lymphocyte subsets have been extensively studied, its impact on NK cell function was unreported prior to this study. We investigated effects of short-term cmvIL-10 exposure on human NK cells and found it substantially enhanced NK cell cytotoxicity through natural cytotoxicity receptors NKp30 and NKp46 as well as through C-type lectin-like receptors NKG2C and NKG2D...
April 9, 2019: Journal of Leukocyte Biology
Ce Tang, Yulia Makusheva, Haiyang Sun, Wei Han, Yoichiro Iwakura
Myeloid C-type lectin receptors (CLRs), which consist of an extracellular carbohydrate recognition domain and intracellular signal transducing motif such as the immunoreceptor tyrosine-based activation motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM), are innate immune receptors primarily expressed on myeloid lineage cells such as dendritic cells (DCs) and Mϕs. CLRs play important roles in host defense against infection by fungi and bacteria by recognizing specific carbohydrate components of these pathogens...
April 9, 2019: Journal of Leukocyte Biology
Hai Zhao, Ridong Feng, Aijun Peng, Gaowei Li, Liangxue Zhou
The overwhelming body of research on regulatory lymphocytes has focused on CD4+ CD25+ Foxp3+ T cells (regulatory T cells); however, the last 5 years have witnessed inspiring progress in our understanding of regulatory B cells, regulatory CD8+ T cells, regulatory γδ cells, and, more recently, regulatory innate lymphoid cells(ILCregs). This review focuses on these so-called noncanonical regulatory cell subsets. We primarily survey existing information on the phenotype, function, sustaining factors, and clinical value of the 4 best-characterized non-CD4 + Foxp3+ T regulatory cells...
April 8, 2019: Journal of Leukocyte Biology
Nirojah Vijitha, Daniel R Engel
Discussion on remote activation of Th17 cells by lung myeloid cells during EAE.
April 8, 2019: Journal of Leukocyte Biology
Meihong Deng, Melanie J Scott, Jie Fan, Timothy R Billiar
High mobility group box 1 (HMGB1) is a multifunctional nuclear protein, probably known best as a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. However, HMGB1 has multiple functions that depend on its location in the nucleus, in the cytosol, or extracellularly after either active release from cells, or passive release upon lytic cell death. Movement of HMGB1 between cellular compartments is a dynamic process induced by a variety of cell stresses and disease processes, including sepsis, trauma, and hemorrhagic shock...
April 4, 2019: Journal of Leukocyte Biology
Silvia De Alessandris, G John Ferguson, Alison J Dodd, Jatinder K Juss, Abhinandan Devaprasad, Siân Piper, Owen Wyatt, Helen Killick, Dominic J Corkill, E Suzanne Cohen, Aridaman Pandit, Timothy R D J Radstake, Rosalind Simmonds, Alison M Condliffe, Matthew A Sleeman, Andrew S Cowburn, Donna K Finch, Edwin R Chilvers
GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFRα) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFRα expression is poorly understood, particularly the role of GM-CSFRα in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFRα surface expression...
April 3, 2019: Journal of Leukocyte Biology
Arshad Khan, Vipul Kumar Singh, Robert L Hunter, Chinnaswamy Jagannath
Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status...
April 2, 2019: Journal of Leukocyte Biology
Kamila Bendíčková, Federico Tidu, Marco De Zuani, Marcela Hortová Kohoutková, Ivana Andrejčinová, Antonio Pompeiano, Silvie Bělášková, Giancarlo Forte, Teresa Zelante, Jan Frič
Calcineurin (CN) inhibitors are effective clinical immunosuppressants but leave patients vulnerable to potentially fatal fungal infections. This study tested the hypothesis that CN inhibition interferes with antifungal immune defenses mediated by monocytes. We showed that NFAT is expressed by human monocytes, and is activated by exposure to fungal ligands. We confirmed that NFAT translocation potently activated target gene transcription using a human monocytic reporter cell line. Inhibition of CN-NFAT by cyclosporine A significantly reduced monocyte production of TNF-α, IL-10, and MCP-1 proteins in response to pattern recognition receptor ligands as well as to Aspergillus fumigatus conidia...
April 1, 2019: Journal of Leukocyte Biology
Alexandra A Vita, Emily A Royse, Nicholas A Pullen
Gut immune system homeostasis involves diverse structural interactions among resident microbiota, the protective mucus layer, and a variety of cells (intestinal epithelial, lymphoid, and myeloid). Due to the substantial surface area in direct contact with an "external" environment and the diversity of xenobiotic, abiotic, and self-interactions coordinating to maintain gut homeostasis, there is enhanced potential for the generation of endogenous danger signals when this balance is lost. Here, we focus on the potential generation and reception of damage in the gut resulting from exposure to nanoparticles (NPs), common food and drug additives...
March 29, 2019: Journal of Leukocyte Biology
Zayda Fonseca, Eileen Uribe-Querol, César Díaz-Godínez, Julio C Carrero, Carlos Rosales
Amoebiasis is an infection of global importance, caused by the eukaryotic parasite Entamoeba histolytica. Pathogenic E. histolytica is associated worldwide with over a million cases of amoebic dysentery, colitis, and amoebic liver abscess. In contrast, the nonpathogenic Entamoeba dispar does not cause these diseases, although it is commonly found in the same areas as pathogenic amoeba. Entamoeba histolytica infection is usually associated with infiltrating neutrophils. These neutrophils appear to play a defensive role against this parasite, by mechanisms not completely understood...
March 26, 2019: Journal of Leukocyte Biology
Kai Xu, Kimberly A Cooney, Eric Y Shin, Lanfang Wang, Juline N Deppen, Sydney C Ginn, Rebecca D Levit
Neutrophil extracellular traps (NETs) are implicated in autoimmune, thrombotic, malignant, and inflammatory diseases; however, little is known of their endogenous regulation under basal conditions. Inflammatory effects of neutrophils are modulated by extracellular purines such as adenosine (ADO) that is inhibitory or ATP that generally up-regulates effector functions. In order to evaluate the effects of ADO on NETs, human neutrophils were isolated from peripheral venous blood from healthy donors and stimulated to make NETs...
March 25, 2019: Journal of Leukocyte Biology
Laura Marongiu, Laura Gornati, Irene Artuso, Ivan Zanoni, Francesca Granucci
TLRs are a class of pattern recognition receptors (PRRs) that detect invading microbes by recognizing pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, TLRs activate a signaling cascade that leads to the production of inflammatory mediators. The localization of TLRs, either on the plasma membrane or in the endolysosomal compartment, has been considered to be a fundamental aspect to determine to which ligands the receptors bind, and which transduction pathways are induced. However, new observations have challenged this view by identifying complex trafficking events that occur upon TLR-ligand binding...
March 22, 2019: Journal of Leukocyte Biology
Marco Túlio R Gomes, Daiane M Cerqueira, Erika S Guimarães, Priscila C Campos, Sergio C Oliveira
The immune system is armed with a broad range of receptors to detect and initiate the elimination of bacterial pathogens. Inflammasomes are molecular platforms that sense a diverse range of microbial insults to develop appropriate host response. In that context, noncanonical inflammasome arose as a sensor for Gram-negative bacteria-derived LPS leading to the control of infections. This review describes the role of caspase-11/gasdermin-D-dependent immune response against Gram-negative bacteria and presents an overview of guanylate-binding proteins (GBPs) at the interface of noncanonical inflammasome activation...
March 21, 2019: Journal of Leukocyte Biology
Haider Rasheed Alrafas, Philip B Busbee, Mitzi Nagarkatti, Prakash S Nagarkatti
Inflammatory diseases of the gastrointestinal tract are often associated with microbial dysbiosis. Thus, dietary interactions with intestinal microbiota, to maintain homeostasis, play a crucial role in regulation of clinical disorders such as colitis. In the current study, we investigated if resveratrol, a polyphenol found in a variety of foods and beverages, would reverse microbial dysbiosis induced during colitis. Administration of resveratrol attenuated colonic inflammation and clinical symptoms in the murine model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
March 21, 2019: Journal of Leukocyte Biology
Rubin N Joshi, Sunjay Jude Fernandes, Ming-Mei Shang, Narsis A Kiani, David Gomez-Cabrero, Jesper Tegnér, Angelika Schmidt
Regulatory T cells (Tregs) act as indispensable unit for maintaining peripheral immune tolerance mainly by regulating effector T cells. T cells resistant to suppression by Tregs pose therapeutic challenges in the treatment of autoimmune diseases, while augmenting susceptibility to suppression may be desirable for cancer therapy. To understand the cell intrinsic signals in T cells during suppression by Tregs, we have previously performed a global phosphoproteomic characterization. We revealed altered phosphorylation of protein phosphatase 1 regulatory subunit 11 (PPP1R11; Inhibitor-3) in conventional T cells upon suppression by Tregs...
March 18, 2019: Journal of Leukocyte Biology
Samreen Sadaf, Abhishek Kumar Singh, Deepika Awasthi, Sheela Nagarkoti, Ashok Kumar Agrahari, Rajeshwar Nath Srivastava, Kumaravelu Jagavelu, Sachin Kumar, Manoj Kumar Barthwal, Madhu Dikshit
Neutrophils play important role in immunity and inflammation through diverse mechanisms. Reports from this lab and others have demonstrated involvement of NO in neutrophil adhesion, chemotaxis, bacterial killing, reactive oxygen species generation, neutrophil extracellular traps' formation, and apoptosis. Constitutive expression of iNOS in human neutrophils has also been documented. The role of NO-iNOS in neutrophil differentiation however remains ill-defined. The present study was undertaken to understand the role of NO generated from iNOS in the neutrophil differentiation by using iNOS-overexpressing K562 cells (K562iNOS ) and iNOS-deficient murine progenitor cells (lineage negative cells; lin-ve )...
March 12, 2019: Journal of Leukocyte Biology
Raed Madhi, Milladur Rahman, Matthias Mörgelin, Henrik Thorlacius
Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c-Abelson (c-Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l-arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c-Abl kinase, citrullinated histone 3, DNA-histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified...
March 12, 2019: Journal of Leukocyte Biology
Jiangping Li, Chenxi Jin, Changyou Wu, Jun Huang
Host-pathogen interactions in tuberculosis (TB) should be studied at the disease sites because Mycobacterium tuberculosis (M.tb) is predominantly contained in local tissue lesions. T-cell immune responses are required to mount anti-mycobacterial immunity. However, T-cell immune responses modulated by programmed cell death protein 1 (PD-1) during tuberculosis pleurisy (TBP) remains poorly understood. We selected the pleural fluid mononuclear cells (PFMCs) from TBP and PBMCs from healthy donors (HD), and characterized PD-1-expresing T-cell phenotypes and functions...
March 12, 2019: Journal of Leukocyte Biology
Vijaykumar S Meli, Praveen K Veerasubramanian, Hamza Atcha, Zachary Reitz, Timothy L Downing, Wendy F Liu
Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate immune cells are capable of recognizing and clearing dead cells and pathogens, and orchestrating inflammatory and healing processes that occur in response to injury. In addition, macrophages are involved in the progression of many inflammatory diseases including cardiovascular disease, fibrosis, and cancer. Although it has long been known that macrophages respond dynamically to biochemical signals in their microenvironment, the role of biophysical cues has only recently emerged...
March 12, 2019: Journal of Leukocyte Biology
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