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Benjamin D Groff, Andrew W L Kinman, Jacob F Woodroof, Rebecca R Pompano
Explants of lymphoid tissue provide a rare opportunity to assess the organization of the immune system in a living, dynamic environment. Traditionally, ex vivo immunostaining is conducted in fixed tissue sections, while live tissues are analyzed using genetically engineered fluorescent reporters or adoptively transferred, pre-labelled cell populations. Here, we validated a protocol for immunostaining and imaging in live, thick slices of lymph node tissue, thus providing a spatial "map" of the lymph node while maintaining the viability and functionality of the slices...
October 18, 2018: Journal of Immunological Methods
Rodolfo Servín-Blanco, Rosa Mariana Chávaro-Ortiz, Rubén Zamora-Alvarado, Fernando Martínez-Cortes, Goar Gevorkian, Karen Manoutcharian
Although various immune checkpoint inhibitors (ICIs), used for the treatment of advanced cancer, showed remarkably durable tumor regression in a subset of patients, there are important limitations in a large group of non-responders, and the generation of novel immunogens capable of inducing protective cellular immune responses is a priority in cancer immunotherapy field. During the last decades, several types of vaccine immunogens have been used in numerous preclinical studies and clinical trials. However, although immunity to tumor Ags can be elicited by most vaccines tested, their clinical efficacy remains modest...
October 16, 2018: Immunology Letters
Stéphanie Humblet-Baron, John S Barber, Carlos Roca, Aurelie Lenaerts, Pandelakis A Koni, Adrian Liston
Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed in both murine studies with constitutive depletion of DCs, and in patients with congenital deficiency in DCs caused by mutations in GATA2 or IRF8 The mechanistic link between DC deficiency and MPD was not predicted through the known biology and has remained an enigma. Prevailing models suggest numerical DC deficiency leads to MPD through compensatory myeloid differentiation...
October 17, 2018: Blood
Decai Tian, Xiaodong Zhu, Rong Xue, Peng Zhao, Yuanrong Yao
History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function...
November 2018: Radiology
Mei Qiu Lim, Emmanuelle A P Kumaran, Hwee Cheng Tan, David C Lye, Yee Sin Leo, Eng Eong Ooi, Paul A MacAry, Antonio Bertoletti, Laura Rivino
Zika virus (ZIKV), a flavivirus with homology to dengue virus (DENV), is spreading to areas of DENV hyper-endemicity. Heterologous T cell immunity, whereby virus-specific memory T cells are activated by variant peptides derived from a different virus, can lead to enhanced viral clearance or diminished protective immunity and altered immunopathology. In mice, CD8+ T cells specific for DENV provide in vivo protective efficacy against subsequent ZIKV infection. In humans, contrasting studies report complete absence or varying degrees of DENV/ZIKV T cell cross-reactivity...
2018: Frontiers in Immunology
Charlotte DE Wolf, Marja VAN DE Bovenkamp, Marcel Hoefnagel
Dendritic cells (DCs) are key connectors between the innate and adaptive immune system and have an important role in modulating other immune cells. Therefore, their therapeutic application to steer immune responses is considered in various disorders, including cancer. Due to differences in the cell source and manufacturing process, each DC medicinal product is unique. Consequently, release tests to ensure consistent quality need to be product-specific. Although general guidance concerning quality control testing of cell-based therapies is available, cell type-specific regulation is still limited...
October 13, 2018: Cytotherapy
Olivier Lucar, Mariama Sadjo Diallo, Charles Bayard, Assia Samri, Nadine Tarantino, Patrice Debré, Rodolphe Thiébaut, Françoise Brun-Vézinet, Sophie Matheron, Rémi Cheynier, Vincent Vieillard
OBJECTIVE: HIV-1 and HIV-2 differ notably in their epidemiology, with worldwide HIV-1 spread and HIV-2 mainly confined to West Africa. Natural killer (NK) cells are critical antiviral effectors of the immune system; however, limited information is available about these innate effector cells during HIV-2 infection. METHOD: In this study, 24 untreated HIV-2-infected patients were analyzed and compared with 21 long-term nonprogressor and 10 controller HIV-1 patients, and healthy donors...
October 15, 2018: AIDS
Andrea Polli, Jessica Van Oosterwijck, Mira Meeus, Luc Lambrecht, Jo Nijs, Kelly Ickmans
Background and aims The interaction between the immune system and pain has been thoroughly explored in the recent decades. The release of inflammatory mediators from immune cells has the capability of activating neurons and glial cells, in turn sensitizing the nervous system. Both immune system alterations and pain modulation dysfunctions have been shown in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following exercise. However, no studies tried to explore whether these two phenomena are linked and can explain exercise-induced symptoms worsening in people with ME/CFS...
October 16, 2018: Scandinavian Journal of Pain
Jeong Eun Song, Bo Ra Sim, Yoo Shin Jeon, Han Sol Kim, Eun Yeong Shin, Cristiano Carlomagno, Gilson Khang
Corneal endothelial cells (CEnCs) play a fundamental role in maintaining the transparency of the cornea. CEnCs lose their full proliferating capacity when tissue damages occur. The loss in proliferation rate is associated with corneal edema and decrease in visual acuity, leading in severe cases, to blindness. In these situations, a corneal transplant is usually needed to restore the original tissue functions. Tissue engineering is an efficient alternative for the production of implantable films, which can regenerate the tissue functions regulating at the same time the immune-response...
October 16, 2018: Journal of Biomaterials Science. Polymer Edition
Julia Y Co, Gerardo Cárcamo-Oyarce, Nicole Billings, Kelsey M Wheeler, Scott C Grindy, Niels Holten-Andersen, Katharina Ribbeck
Mucus is a biological gel that lines all wet epithelia in the body, including the mouth, lungs, and digestive tract, and has evolved to protect the body from pathogenic infection. However, microbial pathogenesis is often studied in mucus-free environments that lack the geometric constraints and microbial interactions in physiological three-dimensional mucus gels. We developed fluid-flow and static test systems based on purified mucin polymers, the major gel-forming constituents of the mucus barrier, to understand how the mucus barrier influences bacterial virulence, particularly the integrity of Pseudomonas aeruginosa biofilms, which can become resistant to immune clearance and antimicrobial agents...
2018: NPJ Biofilms and Microbiomes
Sajal Gupta, Alison Johnson, Simon Meyrick, Angharad P Davies, R Chalmers
Introduction: Cryptosporidium infection is known to cause hepato-biliary involvement, mainly in association with T-cell immune deficiency. Hepato-biliary involvement in association with milder immunosuppression is less well described. We describe the first case, to our knowledge, of Cryptosporidium hominis hepato-biliary infection associated with tacrolimus in a patient with nephrotic syndrome. Case presentation: A 14 year old girl who had been on tacrolimus for nephrotic syndrome presented with diarrhea due to C...
August 2018: JMM Case Reports
Jane Harper, Katherine J Adams, Giovanna Bossi, Debbie E Wright, Andrea R Stacey, Nicole Bedke, Ruth Martinez-Hague, Dan Blat, Laure Humbert, Hazel Buchanan, Gabrielle S Le Provost, Zoe Donnellan, Ricardo J Carreira, Samantha J Paston, Luise U Weigand, Martina Canestraro, Joseph P Sanderson, Sophie Botta Gordon-Smith, Kate L Lowe, Karolina A Rygiel, Alex S Powlesland, Annelise Vuidepot, Namir J Hassan, Brian J Cameron, Bent K Jakobsen, Joseph Dukes
Robust preclinical testing is essential to predict clinical safety and efficacy and provide data to determine safe dose for first-in-man studies. There are a growing number of examples where the preclinical development of drugs failed to adequately predict clinical adverse events in part due to their assessment with inappropriate preclinical models. Preclinical investigations of T cell receptor (TCR)-based immunotherapies prove particularly challenging as these biologics are human-specific and thus the conventional testing in animal models is inadequate...
2018: PloS One
Ho Pan Sham, Mark Bazett, Momir Bosiljcic, Hyungjun Yang, Beryl Luk, Hong T Law, Vijay Morampudi, Hong B Yu, Jim Pankovich, Simon Sutcliffe, Brian Bressler, John K Marshall, Richard N Fedorak, Jenny Chen, Michelle Jones, Hal Gunn, Shirin Kalyan, Bruce A Vallance
Background: Current ulcerative colitis (UC) treatments are focused on symptom management primarily via immune suppression. Despite the current arsenal of immunosuppressant treatments, the majority of patients with UC still experience disease progression. Importantly, aggressive long-term inhibition of immune function comes with consequent risk, such as serious infections and malignancy. There is thus a recognized need for new, safe and effective treatment strategies for people living with UC that work upstream of managing the symptoms of the disease...
2018: Frontiers in Immunology
Liang Shen, Haochen Yu, Ming Liu, Deying Wei, Wei Liu, Changzhong Li, Qin Chang
Purpose: The aim of the present study was to construct a novel long non-coding RNA (lncRNA) signature to predict the prognosis of patients with cervical cancer (CC). Materials and methods: We downloaded lncRNA expression profiles and clinical characteristics from The Cancer Genome Atlas database and randomly divided them into a training dataset (n=200) and a testing dataset (n=87). Using a Cox-based iterative sure independence screening procedure combined with a resampling technique, a lncRNA signature was calculated from prognostic lncRNAs in the training dataset and was independently verified in the testing and the entire datasets...
2018: OncoTargets and Therapy
Yu-Hsing Lin, Jong-Tar Kuo, Yun-Yu Chen, K J Senthil Kumar, Chiu-Ping Lo, Chin-Chung Lin, Sheng-Yang Wang
Taiwanofungus camphoratus is a unique medicinal mushroom endemic to Taiwan, and it is used as a folk medicine in East Asian countries. The aim of the present study was to investigate the immunomodulatory effects of "leader Antrodia cinnamomea capsule" (LAC), a health food product containing solid-state cultivated mycelial powder of T. camphoratus. For the in vivo studies, mice were orally administered LAC (76, 250, and 760 mg/kg b.w.) for 30 days, and its effects on cell-mediated humoral immune function were examined...
2018: International Journal of Medicinal Mushrooms
Virginia Angélica Bianchi, Hendrick Langeloh, Urban Tillmann, Bernd Krock, Annegret Müller, Ulf Bickmeyer, Doris Abele
Multiple toxic and bioactive compounds produced by Alexandrium spp. cause adverse effects on bivalves, but these effects are frequently difficult to attribute to a single compound class. To disentangle the effect of neurotoxic vs lytic secondary metabolites, we exposed blue mussels to either a paralytic shellfish toxin (PST) producing Alexandrium spp. strain, or to an exclusively lytic compound (LC) producing strain, or a strain containing both compound classes, to evaluate the time dependent effects after 3 and 7 days of feeding...
October 11, 2018: Fish & Shellfish Immunology
Junhua Wang, Fadi Jebbawi, Anne-Pauline Bellanger, Guido Beldi, Laurence Millon, Bruno Gottstein
The growth potential of the tumour-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly dependent upon the nature/function of the periparasitic adaptive host immune-mediated processes. PD-1/PD-L1 pathway (Programmed Cell Death 1), which inhibits lymphocytic proliferation in tumour development, is over-expressed at the chronic stage of AE. We tested the impact of a PD-1/PD-L1 pathway blockade on the outcome of both chronic AE (intraperitoneal metacestode inoculation, secondary AE, SAE) and acute AE (peroral egg infection, primary AE, PAE)...
October 13, 2018: Parasite Immunology
Ying Jiang, Zhentang Cao, Huizi Ma, Guihong Wang, Xuemei Wang, Zhan Wang, Yaqin Yang, Huiqing Zhao, Genliang Liu, Longling Li, Tao Feng
According to epidemiologic studies, smoking appears to downregulate the prevalence of Parkinson's disease (PD), possibly due to antiinflammatory mechanisms via activation of α7 nicotinic acetylcholine receptors (α7 nAChRs). This receptor also appears to play a role in T-cell differentiation. Recently, it has become apparent that the innate immune system participates in PD pathogenesis. The aim of this study was to evaluate the effects of auricular vagus nerve stimulation (aVNS) on substantia nigra (SN) dopaminergic neurodegeneration and the associated neuroinflammation and immune responses in a rat PD model...
November 2018: Neurochemical Research
Mei Li Ng, Nagendra S Yarla, Mario Menschikowski, Olga A Sukocheva
Balanced sphingolipid signaling is important for the maintenance of homeostasis. Sphingolipids were demonstrated to function as structural components, second messengers, and regulators of cell growth and survival in normal and disease-affected tissues. Particularly, sphingosine kinase 1 (SphK1) and its product sphingosine-1-phosphate (S1P) operate as mediators and facilitators of proliferation-linked signaling. Unlimited proliferation (self-renewal) within the regulated environment is a hallmark of progenitor/stem cells that was recently associated with the S1P signaling network in vasculature, nervous, muscular, and immune systems...
September 26, 2018: World Journal of Stem Cells
Jiří Hrdý, Kateřina Vlasáková, Viktor Černý, Lenka Súkeníková, Olga Novotná, Petra Petrásková, Kristýna Boráková, Rája Lodinová-Žádníková, Libuše Kolářová, Ludmila Prokešová
The growing knowledge of the key role of microbiota in the maturation of neonatal immune system suggests that manipulation of microbiota could be exploited in hampering allergy development. In this study, Escherichia coli O83:K24:H31 (EcO83) was administered to newborns that were followed prospectively. Several immunological characteristics (cytokines, specific IgE, total T regulatory cells (Treg) and subpopulation of natural Treg (nTreg) and induced Treg (iTreg)) were tested in peripheral blood of eight year old children...
October 10, 2018: European Journal of Immunology
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