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Immunology and Cell Biology

Seyed Mohammad Gheibi Hayat, Vanessa Bianconi, Matteo Pirro, Amirhossein Sahebkar
During the life of a human being several tons of apoptotic cells and debris are produced. These apoptotic particles should be cleared quickly and accurately from the body, as they may lose their membrane integrity with the probability of leakage of cytotoxic materials and other intracellular antigens into the environment. The action of removing apoptotic particles occurs by a process called efferocytosis. Efferocytosis is a highly regulated balance among a set of find-me, eat-me and don't-eat-me signals. Efferocytosis is accompanied by a suppression of the immune system that can explain its negative role in cancer...
September 19, 2018: Immunology and Cell Biology
Ailin Lepletier, Viviana P Lutzky, Deepak Mittal, Kimberley Stannard, Thomas S Watkins, Champa N Ratnatunga, Corey Smith, Helen M McGuire, Roslyn A Kemp, Pamela Mukhopadhyay, Nicola Waddell, Mark J Smyth, William C Dougall, John J Miles
CD96 has recently been shown to be a potent immune checkpoint molecule in mice but a similar role in humans is unknown. In this study we provide a detailed map of CD96 expression across human lymphocyte lineages, the kinetics of CD96 regulation upon T cell activation and co-expression with other conventional and emerging immune checkpoint molecules. We show that CD96 is predominantly expressed by T cells and has a unique lymphocyte expression profile. CD96high T cells exhibited distinct effector functions upon activation...
September 17, 2018: Immunology and Cell Biology
Yi Yang, Di Sun, Ji Zhou, Chensheng Tan, Hong Zhang, ZhengRong Chen, ChuangLi Hao, Jinping Zhang
Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T cell function. In mice, MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have shown that injection of a lethal or sublethal dose of LPS into mice could result in the expansion of MDSCs in the bone marrow(BM), spleen and blood. Until now, the molecular mechanisms responsible for this expansion are poorly studied; specifically, the roles of the individual microRNAs (miRNAs) which may be involved remain largely unknown...
September 17, 2018: Immunology and Cell Biology
Gina J Fiala, Bruno Silva-Santos
No abstract text is available yet for this article.
September 16, 2018: Immunology and Cell Biology
Katarzyna Mikolajewicz, Grzegorz Chodaczek
Several tissue clearing methods have been developed for three-dimensional imaging of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole-mounted vaginal wall to reveal spatial distribution of γδ T lymphocytes - the key cells engaged in the epithelial homeostasis control and immune surveillance. Both methods rendered the tissue transparent and enabled detection of the green fluorescent protein (GFP) expressing γδ T cells in vaginal samples of Tcrd-H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC preserved GFP signal and allowed for cell localization assessment during the estrous cycle...
September 14, 2018: Immunology and Cell Biology
Chenming Wu, Ang Li, Jian Hu, Jiuhong Kang
The role of specific histone deacetylase (HDAC) proteins in regulating the lipopolysaccharide (LPS)-induced inflammatory response and its underlying mechanisms are unclear. Here, HDAC2, a class I HDAC family protein, is essential for the LPS-triggered inflammatory response in macrophages. LPS stimulation increases HDAC2 expression in macrophages. Knockdown of HDAC2 decreases the expression of proinflammatory genes, such as IL-12, TNF-α and iNOS following stimulation with LPS. The adoptive transfer of HDAC2 knockdown macrophages attenuates the LPS-triggered innate inflammatory response in vivo, and these mice are less sensitive to endotoxin shock and Escherichia coli-induced sepsis...
September 12, 2018: Immunology and Cell Biology
Juming Yan, Daniel J Cua, Michele Wl Teng
No abstract text is available yet for this article.
September 8, 2018: Immunology and Cell Biology
Jane A Mullaney, Juliette E Stephens, Brooke E Geeling, Emma E Hamilton-Williams
The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible non-obese diabetic (NOD) mice have been shown to harbour a distinct microbiota to disease protected mice. We hypothesised that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6 derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice...
September 7, 2018: Immunology and Cell Biology
Pierre C McCarthy, Iain R Phair, Corinna Greger, Katerina Pardali, Victoria A McGuire, Andrew R Clark, Matthias Gaestel, J Simon C Arthur
IL-33 is an IL-1-related cytokine that can act as an alarmin when released from necrotic cells. Once released it can target various immune cells including mast cells, innate lymphoid cells and T cells to elicit a Th2-like immune response. We show here that bone marrow derived mast cells produce IL-13, IL-6, TNF, GM-CSF, CCL3 and CCL4 in response to IL-33 stimulation. Inhibition of the p38 MAPK, or inhibition or knockout of its downstream kinases MK2 and MK3, blocked the production of these cytokines in response to IL-33...
September 1, 2018: Immunology and Cell Biology
Hazel C Poyntz, Angela Jones, Ruy Jauregui, Wayne Young, Aurélie Gestin, Anna Mooney, Olivier Lamiable, Eric Altermann, Alfonso Schmidt, Olivier Gasser, Laura Weyrich, Chris J Jolly, Michelle A Linterman, Graham Le Gros, Edwin D Hawkins, Elizabeth Forbes-Blom
Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes...
August 28, 2018: Immunology and Cell Biology
Cyril Seillet, Elysa Carr, Derek Lacey, Michael D Stutz, Marc Pellegrini, Lachlan Whitehead, Joel Rimes, Edwin D Hawkins, Ben Roediger, Gabrielle T Belz, Philippe Bouillet
BPSM1 (Bone phenotype spontaneous mutant 1) mice develop severe polyarthritis and heart valve disease as a result of a spontaneous mutation in the Tnf gene. In these mice, the insertion of a retrotransposon in the 3' untranslated region of Tnf causes a large increase in the expression of the cytokine. We have found that these mice also develop inducible bronchus-associated lymphoid tissue (iBALT), as well as nodular lymphoid hyperplasia (NLH) in the bone marrow. Loss of TNFR1 prevents the development of both types of follicles, but deficiency of TNFR1 in the hematopoietic compartment only prevents the iBALT and not the NLH phenotype...
August 14, 2018: Immunology and Cell Biology
Xiaomin Guo, Huan Wang, Yang Li, Xiaopeng Leng, Weiwei Huang, Yanbing Ma, Tao Xu, Xiaopeng Qi
The commercial transfection reagent Lipofectamine has been widely used for cytoplasmic delivery of nucleic acids and for cytosolic engagement with intracellular innate immune sensors to trigger type I interferon (IFN) production. However, the effect of Lipofectamine alone on type I IFN response has not been studied in detail. Here, we show that Lipofectamine induced type I IFN signaling in both RAW 264.7 macrophage-like cells and primary bone marrow-derived macrophages. Type I IFN induction was dependent on interferon regulatory factor (IRF)3 and IRF7 and partially required the toll/interleukin-1 receptor-domain-containing adapter-inducing interferon-β...
August 6, 2018: Immunology and Cell Biology
Sara J Thygesen, Karli E Takizawa, Avril A B Robertson, David P Sester, Katryn J Stacey
Inflammasomes are protein complexes activated by infection and cellular stress that promote caspase-1 activation and subsequent inflammatory cytokine processing and cell death. It has been anticipated that inflammasome activity contributes to autoimmunity. However, we previously showed that macrophages from autoimmune New Zealand Black (NZB) mice lack NLRP3 inflammasome function, and their absent in melanoma 2 (AIM2) inflammasome responses are compromised by high expression of the AIM2 antagonist protein p202...
July 27, 2018: Immunology and Cell Biology
Weidang Li, Pareesha Gudipaty, Chuxi Li, Kyle K Henderson, Kyle H Ramsey, Ashlesh K Murthy
We have shown previously that intranasal vaccination with recombinant chlamydial protease-like activity factor (rCPAF: antigen) and interleukin-12 (IL-12) as an adjuvant induces robust protection against pathological consequences of female genital tract infection with Chlamydia muridarum, a closely related species and a rodent model for the human pathogen Chlamydia trachomatis. Another related species Chlamydia pneumoniae, a human respiratory pathogen, has been associated with exacerbation of atherosclerotic pathology...
July 27, 2018: Immunology and Cell Biology
Melanie J McConnell
No abstract text is available yet for this article.
July 20, 2018: Immunology and Cell Biology
Kyle Malone, Sylvie Amu, Anne C Moore, Christian Waeber
Stroke is a major cause of morbidity and mortality worldwide. Despite the intensive search for new therapies, hundreds of agents targeting various pathophysiological mechanisms have failed clinical trials, and the thrombolytic agent tissue plasminogen activator is currently the only FDA-approved medication for the treatment of acute ischemic stroke. The immune system is involved in all stages of stroke, from the pathogenesis of risk factors to neurotoxicity, to tissue remodeling and repair. There is a bidirectional interaction between the brain and the immune system, with stroke-induced immunosuppression and subsequent infection a principal source of patient mortality...
July 19, 2018: Immunology and Cell Biology
Natalie J Bitto, Paul J Baker, Jennifer K Dowling, Georgie Wray-McCann, Amanda De Paoli, Le Son Tran, Pak Ling Leung, Katryn J Stacey, Ashley Mansell, Seth L Masters, Richard L Ferrero
Outer membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria both in vivo and in vitro. These lipid-bound structures carry a range of immunogenic components derived from the parent cell, which are transported into host target cells and activate the innate immune system. Recent advances in the field have shed light on some of the multifaceted roles of OMVs in host-pathogen interactions. In this study, we investigated the ability of OMVs from two clinically important pathogens, Pseudomonas aeruginosa and Helicobacter pylori, to activate canonical and noncanonical inflammasomes...
July 12, 2018: Immunology and Cell Biology
Anne C La Flamme
No abstract text is available yet for this article.
July 10, 2018: Immunology and Cell Biology
Rachael Keating, Melissa Y Morris, Wen Yue, Cory E Reynolds, Tarsha L Harris, Scott A Brown, Peter C Doherty, Paul G Thomas, Maureen A McGargill
Current influenza A virus (IAV) vaccines stimulate antibody responses that are directed against variable regions of the virus, and are therefore ineffective against divergent strains. As CD8+ T cells target the highly conserved, internal IAV proteins, they have the potential to increase heterosubtypic immunity. Early T-cell priming events influence lasting memory, which is required for long-term protection. However, the early responding, IAV-specific cells are difficult to monitor because of their low frequencies...
July 4, 2018: Immunology and Cell Biology
Radomir Kratchmarov, Sara Viragova, Min Jung Kim, Nyanza J Rothman, Kang Liu, Boris Reizis, Steven L Reiner
Growth signals drive hematopoietic progenitor cells to proliferate and branch into divergent cell fates, but how unequal outcomes arise from a common progenitor is not fully understood. We used steady-state analysis of in vivo hematopoiesis and Fms-related tyrosine kinase 3 ligand (Flt3L)-induced in vitro differentiation of dendritic cells (DCs) to determine how growth signals regulate lineage bias. We found that Flt3L signaling induced anabolic activation and proliferation of DC progenitors, which was associated with DC differentiation...
September 2018: Immunology and Cell Biology
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