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Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Melissa Frick, Pierre Mouchacca, Grégory Verdeil, Yannick Hamon, Cyrille Billaudeau, Michel Buferne, Mathieu Fallet, Nathalie Auphan-Anezin, Anne-Marie Schmitt-Verhulst, Claude Boyer
Cancer-germline genes in both human and mice have been shown to encode antigens susceptible to targeting by cytotoxic CD8 T effector cells (CTL). We analyzed the ability of CTL to kill different tumor cell lines expressing the same cancer-germline gene P1A (Trap1a). We previously demonstrated that CTL expressing a TCR specific for the P1A35-43 peptide associated with H-2L(d) , although able to induce regression of P1A-expressing P815 mastocytoma cells, were much less effective against P1A-expressing melanoma cells...
October 7, 2016: Immunology
Mario Rodríguez, Saioa Márquez, Juan Vladimir de la Rosa, Sara Alonso, Antonio Castrillo, Mariano Sánchez Crespo, Nieves Fernández
CREB and STAT3 may control inflammation by several mechanisms, one of the best characterized is the induction of the expression of the anti-inflammatory cytokine IL-10. STAT3 also down-regulates the production of pro-inflammatory cytokines induced by ITAM-coupled receptors, a mechanism termed cross-inhibition. Because signaling via ITAM-dependent mechanisms is a hallmark of fungal pattern receptors, STAT3 activation might be involved in the cross-inhibition associated with invasive fungal infections. The fungal surrogate zymosan produced the phosphorylation of Y705-STAT3 and the expression of Ifnb1 and Socs3, but did not induce the IFN-signature cytokines Cxcl9 and Cxcl10 in BM-derived dendritic cells...
October 6, 2016: Immunology
Claire L Feerick, Declan P McKernan
NOD-like receptors (NLRs) are a family of 23 receptors known as pattern recognition receptors (PRRs), they are expressed in many cell types and play a key role in the innate immune response. The NLRs are activated by pathogen associated molecular patterns (PAMPs) which include structurally conserved molecules present on the surfaces of bacteria. The activation of these NLRs by pathogens results in the downstream activation of signalling kinases and transcription factors, culminating in the transcription of genes coding for pro-inflammatory factors...
October 5, 2016: Immunology
Louise Sjökvist Ottsjö, Frida Jeverstam, Linda Yrlid, Alexander U Wenzel, Anna K Walduck, Sukanya Raghavan
There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, a chronic infection that can lead to peptic ulcers and gastric cancer in a sub-population of infected individuals. Mucosal CD4(+) T cell responses have been shown to be essential for vaccine-induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4(+) T cell priming to H. pylori antigens...
September 27, 2016: Immunology
Emma Reeves, Edward James
The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8(+) cytotoxic and CD4(+) helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8(+) cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4(+) T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response...
September 23, 2016: Immunology
Viqar Showkat Banday, Kristina Lejon
Although Type 1 diabetes (T1D) is T cell mediated disease in the effector stage, the mechanism behind the initial β cell assault less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in T1D patients prior to disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD...
September 21, 2016: Immunology
Emily B Wong, Thumbi Ndung'u, Victoria O Kasprowicz
Mucosal associated invariant T (MAIT) cells are donor-unrestricted lymphocytes that are surprisingly abundant in humans, representing 1-10% of circulating T cells and further enriched in mucosal tissues. MAIT cells recognize and are activated by small molecule ligands produced by microbes and presented by MR1, a highly conserved MHC-related antigen presenting protein that is ubiquitously expressed in human cells. Increasing evidence suggests that MAIT cells play a protective role in anti-bacterial immunity at mucosal interfaces...
September 16, 2016: Immunology
Helioswilton Sales-Campos, Patrícia R de Souza, Paulo J Basso, Viviani Nardini, Angelica Silva, Fernanda Banquieri, Vanessa B F Alves, Javier E L Chica, Auro Nomizo, Cristina R B Cardoso
The clinical benefits of short-term therapy with glucocorticoids (GC) in patients with inflammatory bowel disease (IBD) are widely known. However, the effects of this treatment towards the re-establishment of the regulatory network in IBD are not fully explored. We have evaluated the immunological effects of the abbreviated GC therapy in experimental colitis induced by 3% dextran sulphate sodium in C57BL/6 mice. Treatment with GC improved disease outcome, constrained circulating leucocytes and ameliorated intestinal inflammation...
September 12, 2016: Immunology
Rhiannon Kundu, Aikaterini Theodoraki, Carolin T Haas, Yanjing Zhang, Benjamin Chain, Janos Kriston-Vizi, Mahdad Noursadeghi, Bernard Khoo
Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene-specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS)...
September 8, 2016: Immunology
Joanna R Ghali, Maliha A Alikhan, Stephen R Holdsworth, A Richard Kitching
Regulatory T (Treg) cells are a suppressive CD4(+) T-cell subset. We generated induced Treg (iTreg) cells and explored their therapeutic potential in a murine model of rapidly progressive glomerulonephritis. Polyclonal naive CD4(+) T cells were cultured in vitro with interleukin-2 (IL-2), transforming growth factor-β1, all-trans-retinoic acid and monoclonal antibodies against interferon-γ and IL-4, generating Foxp3(+) iTreg cells. To enhance their suppressive phenotype, iTreg cultures were modified with the addition of a monoclonal antibody against IL-12p40 or by using RORγt(-/-) CD4(+) T cells...
September 8, 2016: Immunology
Maria Elena Bravo-Adame, Rosario Vera-Estrella, Bronwyn J Barkla, Cecilia Martínez-Campos, Angel Flores-Alcantar, Jose Pablo Ocelotl-Oviedo, Gustavo Pedraza-Alva, Yvonne Rosenstein
CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR)...
September 8, 2016: Immunology
Rani Singh, Tommy Hui, Aritsune Matsui, Ziyad Allahem, Christopher D Johnston, Montserrat Ruiz-Torruella, Susan R Rittling
Osteopontin (OPN) is a pro-inflammatory protein that paradoxically protects against inflammation and bone destruction in a mouse model of endodontic infection. Here we have tested the hypothesis that this effect of OPN is mediated by effects on migration of innate immune cells to the site of infection. Using the air pouch as a model of endodontic infection in mice, we showed that neutrophil accumulation at the site of infection with a mixture of endodontic pathogens is significantly reduced in OPN-deficient mice...
September 6, 2016: Immunology
Hirofumi Tsuzuki, Yojiro Arinobu, Kohta Miyawaki, Ayako Takaki, Shun-Ichiro Ota, Yuri Ota, Hiroki Mitoma, Mitsuteru Akahoshi, Yasuo Mori, Hiromi Iwasaki, Hiroaki Niiro, Hiroshi Tsukamoto, Koichi Akashi
Interleukin-33 (IL-33) induces Th2 cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity-mediated allergic inflammation. Allergy-related innate myeloid cells such as eosinophils, basophils and mast cells express the IL-33 receptor (IL-33R), but it is still unknown how IL-33 regulates allergic inflammation involving these cells and their progenitors. Here, we revealed that the functional IL-33R was expressed on eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs)...
August 29, 2016: Immunology
Lutz Walter, Beatrix Petersen
The killer immunoglobulin-like receptors (KIR) as well as their MHC class I ligands display enormous genetic diversity and polymorphism in macaque species. Signals resulting from interaction between KIR or CD94/NKG2 receptors and their cognate MHC class I proteins essentially regulate the activity of natural killer (NK) cells. Macaque and human KIR share many features, such as clonal expression patterns, gene copy number variations, specificity for particular MHC class I allotypes, or epistasis between KIR and MHC class I genes that influence susceptibility and resistance to immunodeficiency virus infection...
August 27, 2016: Immunology
Didem Ozkazanc, Digdem Yoyen-Ermis, Ece Tavukcuoglu, Yahya Buyukasik, Gunes Esendagli
To cope with immune responses, tumor cells implement elaborate strategies such as adaptive resistance and induction of T cell exhaustion. T cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of costimulatory molecules to T cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukemia-derived costimulatory signals on CD4(+) helper T (Th) cell exhaustion which may limit anti-tumor immunity...
August 27, 2016: Immunology
Frederick S Varn, David W Mullins, Hugo Arias-Pulido, Steven Fiering, Chao Cheng
The role of the immune system in shaping cancer development and patient prognosis has recently become an area of intense focus in industry and academia. Harnessing the adaptive arm of the immune system for tumor eradication has shown great promise in a variety of tumor types. Differences between tissues, however, necessitate a greater understanding of the adaptive immunity programs that are active within each tumor type. In breast cancer, adaptive immune programs play diverse roles depending on the cellular infiltration found in each tumor...
August 26, 2016: Immunology
Hua Rong, Hongjie Shen, Yueli Xu, Hai Yang
Autoimmune uveitis is an intraocular inflammatory disorder in developed countries. Understanding the mechanisms underlying the development and modulation of immune reaction in uveitic eyes is critical for designing therapeutic interventions. Here we investigated the role of Notch signaling in regulatory T cell (Treg cell) function during experimental autoimmune uveitis (EAU). Using the Foxp3-GFP reporter mouse strain, the significance of Notch signaling for the function of infiltrating Treg cells was characterized in an EAU model...
August 26, 2016: Immunology
Ren-Peng Zhou, Xiao-Shan Wu, Ya-Ya Xie, Bei-Bei Dai, Wei Hu, Jin-Fang Ge, Fei-Hu Chen
Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is characterized by chronic, synovial inflammation affecting multiple joints, finally leading to extra articular lesions for which limited effective treatment options are currently available. Interleukin-34 (IL-34), recently discovered as the second colony-stimulating factor-1 receptor (CSF-1R) ligand, is a newly discovered cytokine. Accumulating evidence has disclosed crucial roles of IL-34 in proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis, and inflammation...
August 23, 2016: Immunology
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