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Immune tolerance

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https://www.readbyqxmd.com/read/28922497/mutual-independence-of-alkaline-and-calcium-mediated-signalling-in-aspergillus-fumigatus-refutes-the-existence-of-a-conserved-druggable-signalling-nexus
#1
Omar Loss, Margherita Bertuzzi, Yu Yan, Natalie Fedorova, Bethany L McCann, Darius Armstrong-James, Eduardo A Espeso, Nick D Read, William C Nierman, Elaine M Bignell
Functional coupling of calcium- and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca(2+) , such that highly conserved regulators of both calcium- (Crz) and pH- (PacC/Rim) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti-infectives, abrogation of alkaline signalling has therefore been postulated as an adjunctive antifungal strategy...
September 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28921638/graft-infiltrating-pd-l1-hi-cross-dressed-dendritic-cells-regulate-anti-donor-t-cell-responses-in-mouse-liver-transplant-tolerance
#2
Yoshihiro Ono, Angelica Perez-Gutierrez, Toshimasa Nakao, Helong Dai, Geoffrey Camirand, Osamu Yoshida, Shinichiro Yokota, Donna Beer Stolz, Mark A Ross, Adrian E Morelli, David A Geller, Angus W Thomson
While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#3
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28920148/differential-gene-expression-profiles-and-alternative-isoform-regulations-in-gill-of-nile-tilapia-in-response-to-acute-hypoxia
#4
Hong Lian Li, Hao Ran Lin, Jun Hong Xia
Fish often encounters exposures to acute environmental hypoxia either spatially or temporally. Gill organ plays important roles in response to hypoxic stress in fish. Few studies focus on the molecular regulation mechanisms of gills under hypoxic stress. In this study, we investigated the transcriptomic response to 12-h acute hypoxia in gill of a hypoxia tolerant fish, Nile tilapia Oreochromis niloticus through RNA sequencing (RNA-Seq). We sequenced messenger RNA from three control samples and three hypoxia-treated samples...
September 18, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28920105/the-impact-of-von-willebrand-factor-on-factor-viii-memory-immune-responses
#5
Juan Chen, Jocelyn A Schroeder, Xiaofeng Luo, Qizhen Shi
Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#6
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28916903/merkel-cell-carcinoma-epidemiology-pathogenesis-diagnosis-and-therapy
#7
REVIEW
Teresa Amaral, Ulrike Leiter, Claus Garbe
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a neuroendocrine phenotype. Incidence varies according to the geographic regions but is overall increasing. Different risk factors have been identified namely advanced age, immunosuppression, and ultraviolet light exposure. An association between MCC and polyomavirus infection is known. However, the exact mechanism that leads to carcinogenesis is yet to be fully understood. Surgery when feasible is the recommended treatment for localized disease, followed by adjuvant radiation or chemoradiation...
September 16, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28916147/microbial-associates-of-the-southern-mole-cricket-scapteriscus-borellii-are-highly-pathogenic
#8
Sudarshan K Aryal, Derreck Carter-House, Jason E Stajich, Adler R Dillman
We report the isolation and identification of seven bacterial strains and one fungal strain from dead and diseased Scapteriscus borellii mole crickets collected from a golf course in southern California. Using 16S and 18S rRNA gene sequence analysis we identified the microbes as Serratia marcescens (red), S. marcescens (white), S. marcescens (purple), Achromobacter xylosoxidans, Chryseobacterium sp., Ochrobactrum anthropi, Tsukamurella tryosinosolvens, and Beauveria bassiana. We performed a dose response curve for each of these cricket-associated microbial strains (except T...
September 12, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28916112/a-novel-mimovirus-encoding-chga10-19-peptide-with-pd-l1-induces-t-cell-tolerance-and-ameliorates-the-severity-of-diabetes
#9
Hong Sun, Xiaoguang Han, Xiuhui Yan, Jingli Xu, Qiujing Huang, Fanqing Meng, Hongjin Zhang, Shufa Li
Related studies demonstrate that type 1 diabetes (T1D) is caused by β-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28914372/the-role-of-gut-microbiota-in-the-pathogenesis-of-rheumatic-diseases
#10
Danli Zhong, Chanyuan Wu, Xiaofeng Zeng, Qian Wang
Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses...
September 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28914206/mesenchymal-stem-cell-as-a-potential-therapeutic-for-inflammatory-bowel-disease-myth-or-reality
#11
Sanjucta Adak, Sayani Mukherjee, Dwaipayan Sen
BACKGROUND: Inflammatory bowel diseases (IBD), which include Crohn's disease and Ulcerative Colitis, are inflammatory autoimmune diseases which severely affect the quality of life. Till date, no long-lasting cure has been found for the disease and all the current treatment strategies are mainly focused on dampening the symptomatic inflammatory process that has certain side effects. In addition, a large number of patients remain refractory to conventional therapies. Mesenchymal stem cells (MSCs) can be looked upon as a biodrug to treat IBD owing to their immune-suppressive and regenerative capabilities...
September 13, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28913556/high-dose-vitamin-d3-supplementation-decreases-the-number-of-colonic-cd103-dendritic-cells-in-healthy-subjects
#12
Nina Friis Bak, M Bendix, S Hald, L Reinert, M K Magnusson, J Agnholt
PURPOSE: Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103(+)DCs of high-dose vitamin D3 treatment in healthy subjects. METHODS: Ten healthy subjects received a total of 480,000 IU oral vitamin D3 over 15 days and colonic biopsies were obtained before and after intervention by endoscopy...
September 14, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28912872/preclinical-trial-of-the-multi-targeted-lenvatinib-in-combination-with-cellular-immunotherapy-for-treatment-of-renal-cell-carcinoma
#13
Chengkuan Cai, Jingyuan Tang, Baixin Shen, Liucheng Ding, Yunpeng Shao, Zhengsen Chen, Yinchao Ma, Haoliang Xue, Zhongqing Wei
Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor β, RET and KIT. Cellular immunotherapy has the potential to be a highly targeted treatment, with low toxicity to normal tissues and a high capacity to eradicate tumor tissue. The present study assessed the safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lenvatinib and cellular immunotherapy in a murine model of renal cell carcinoma (RCC)...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28910785/oral-tolerization-with-mycobacterial-heat-shock-protein-65-reduces-chronic-experimental-atherosclerosis-in-aged-mice
#14
Cecilia Wick, Elisabeth Onestingel, Egon Demetz, Hermann Dietrich, Georg Wick
BACKGROUND: Atherosclerosis is a chronic inflammatory disease of the artery wall where both innate and adaptive immunity play important roles. Modulation of the immune response against the stress protein antigen, heat shock protein (HSP) 60, by administration of mycobacterial HSP65 (mbHSP65) orally and/or nasally shows promising therapeutic results in young animals in the sense of less severe experimental atherosclerosis; however, the case of aged animals with already established atherosclerosis has so far never been investigated...
September 15, 2017: Gerontology
https://www.readbyqxmd.com/read/28910563/safety-and-immunogenicity-of-the-killed-bivalent-o1-and-o139-whole-cell-cholera-vaccine-in-the-philippines
#15
Maria Rosario Z Capeding, Maria Liza Antoinette M Gonzales, Mandeep Singh Dhingra, Naveena Aloysia D'cor, Venkat Jayanth Midde, Badri Narayan Patnaik, Yaël Thollot, Eric Desauziers
The killed bivalent (O1 and O139) whole cell oral cholera vaccine (OCV) (Shanchol™) was first licensed in India in 2009 and World Health Organization pre-qualified in 2011. We assessed the safety and immunogenicity of this OCV in the Philippines. This was a phase IV, single-arm, descriptive, open-label study. We recruited 336 participants from two centers: 112 participants in each age group (1-4, 5-14 and ≥15 years). Participants received two OCV doses 14 days apart. Safety was monitored throughout the trial...
September 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#16
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
September 14, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28904345/v%C3%AE-2-t-cell-response-to-malaria-correlates-with-protection-from-infection-but-is-attenuated-with-repeated-exposure
#17
Prasanna Jagannathan, Fredrick Lutwama, Michelle J Boyle, Felistas Nankya, Lila A Farrington, Tara I McIntyre, Katherine Bowen, Kate Naluwu, Mayimuna Nalubega, Kenneth Musinguzi, Esther Sikyomu, Rachel Budker, Agaba Katureebe, John Rek, Bryan Greenhouse, Grant Dorsey, Moses R Kamya, Margaret E Feeney
Vδ2(+) γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2(+) T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2(+) counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904191/the-dose-of-retroviral-infection-determines-the-induction-of-anti-viral-nk-cell-responses
#18
Elisabeth Littwitz-Salomon, Simone Schimmer, Ulf Dittmer
Natural killer (NK) cells are part of the innate immune system and recognize virus-infected cells as well as tumor cells. Conflicting data about the beneficial or even detrimental role of NK cells in different infectious diseases were described. While the type of pathogen strongly influences NK cell functionality, less is known about how the infection dose influences the quality of a NK cell response against retroviruses. Here we used the well-established Friend retrovirus (FV) mouse model to investigate the impact of virus dose on the induction of anti-viral NK cell functions...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28904123/unveiling-the-peptide-motifs-of-hla-c-and-hla-g-from-naturally-presented-peptides-and-generation-of-binding-prediction-matrices
#19
Moreno Di Marco, Heiko Schuster, Linus Backert, Michael Ghosh, Hans-Georg Rammensee, Stefan Stevanović
The classical HLA-C and the nonclassical HLA-E and HLA-G molecules play important roles both in the innate and adaptive immune system. Starting already during embryogenesis and continuing throughout our lives, these three Ags exert major functions in immune tolerance, defense against infections, and anticancer immune responses. Despite these important roles, identification and characterization of the peptides presented by these molecules has been lacking behind the more abundant HLA-A and HLA-B gene products...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28902773/reduced-tcr-signalling-contributes-to-impaired-th17-responses-in-tolerant-kidney-transplant-recipients
#20
Estefania Nova-Lamperti, Marco Romano, Sofia Christakoudi, Manohursingh Runglall, Reuben McGregor, Paula Mobillo, Yogesh Kamra, Tjir-Li Tsui, Sonia Norris, Susan John, Dominic A Boardman, Robert I Lechler, Giovanna Lombardi, Maria P Hernandez-Fuentes
BACKGROUND: The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance. METHODS: CD4T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers...
September 12, 2017: Transplantation
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