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https://www.readbyqxmd.com/read/28640587/silica-nanoparticle-as-a-lymph-node-targeting-platform-for-vaccine-delivery
#1
Myunggi An, Meng Li, Jingchao Xi, Haipeng Liu
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen co-loaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28633932/%C3%AE-2-adrenoreceptor-stimulation-dampens-the-lps-induced-m1-polarization-in-pig-macrophages
#2
Elodie Bacou, Karine Haurogné, Marie Allard, Grégoire Mignot, Jean-Marie Bach, Julie Hervé, Blandine Lieubeau
The cross-talk between sympatho-adreno-medullar axis and innate immunity players was mainly studied in rodents. In intensive husbandry, pigs are exposed to multiple stressors inducing repeated releases of catecholamines that bind to adrenoreceptors (AR) on target cells. Among adrenoreceptors, the β2-AR is largely expressed by immune cells including macrophages. We report herein on the effects of catecholamines, through β2-AR stimulation, on pig macrophage functions activated by LPS. β2-AR stimulation of porcine macrophages prevented the LPS-induced increase in TNFα and IL-8 secretion while increasing IL-10 secretion...
June 17, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#3
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28628715/overcoming-the-resistance-of-pancreatic-cancer-to-immune-checkpoint-inhibitors
#4
REVIEW
Richard A Skelton, Ammar Javed, Lei Zheng, Jin He
Immunotherapy has become a new modality of cancer treatment, but has had a limited success in treating PDAC. A combination approach to immunotherapy, using both immune checkpoint inhibitors and immune activating agonists, is needed, as PDAC does not respond to single-agent checkpoint inhibitors. Studies have also supported using vaccine-based therapies to prime the tumor microenvironment of PDAC with effector T-cells. Other therapeutic strategies including epigenetic agents, stroma modulators, radiotherapy, and T-cell transfer therapies may also prime the tumor microenvironment to overcome resistance to immune checkpoint inhibitors...
June 19, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28625441/the-protective-effects-of-dexmedetomidine-on-ischemic-brain-injury-a-meta-analysis
#5
REVIEW
Lianxiang Jiang, Meizhu Hu, Yan Lu, Ya Cao, Yan Chang, Zeping Dai
BACKGROUND: Intracranial lesions, trauma or surgery-related damage activate immune inflammation and neuroendocrine responses, causing ischemic brain injury. Studies have shown that inflammatory cascade mediated by neuroendocrine hormones and proinflammatory mediators is implicated in the pathophysiology of ischemic brain injury. Alpha2-adrenoceptor agonists, dexmedetomidine, is widely used as neuroprotectants in anesthesia practice. However, it is still lack of a comprehensive meta-analysis to evaluate the neuroprotection of dexmedetomidine against ischemic brain injury via suppressing these two physiological responses...
August 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#6
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28622575/protein-nanoparticle-vaccine-based-on-flagellin-carrier-fused-to-influenza-conserved-epitopes-confers-full-protection-against-influenza-a-virus-challenge
#7
Lei Deng, Jong R Kim, Timothy Z Chang, Han Zhang, Teena Mohan, Julie A Champion, Bao-Zhong Wang
Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi)...
June 13, 2017: Virology
https://www.readbyqxmd.com/read/28621686/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#8
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620379/neuroimmune-interactions-in-schizophrenia-focus-on-vagus-nerve-stimulation-and-activation-of-the-alpha-7-nicotinic-acetylcholine-receptor
#9
REVIEW
Fabiana Maria das Graças Corsi-Zuelli, Fernanda Brognara, Gustavo Fernando da Silva Quirino, Carlos Hiroji Hiroki, Rafael Sobrano Fais, Cristina Marta Del-Ben, Luis Ulloa, Helio Cesar Salgado, Alexandre Kanashiro, Camila Marcelino Loureiro
Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620298/anti-tumor-activity-of-toll-like-receptor-7-agonists
#10
REVIEW
Huju Chi, Chunman Li, Flora Sha Zhao, Li Zhang, Tzi Bun Ng, Guangyi Jin, Ou Sha
Toll-like receptors (TLRs) are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28615443/control-of-immune-mediated-pathology-via-the-aryl-hydrocarbon-receptor
#11
Michael A Wheeler, Veit Rothhammer, Francisco J Quintana
Genetic and environmental factors contribute to the development of immune-mediated diseases. While numerous genetic factors contributing to autoimmunity have been identified in recent years, our knowledge on environmental factors contributing to the pathogenesis of autoimmune diseases and the mechanisms involved is still limited. In this context, the diet, geographical location, environmental pollutants, as well as microbial metabolites have been shown to modulate autoimmune disease development. These environmental factors interact with cellular components of the immune system in distinct and defined ways and are capable of influencing immune responses at the transcriptional and protein level...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615418/cutting-edge-activation-of-sting-in-t-cells-induces-type-i-ifn-responses-and-cell-death
#12
Bridget Larkin, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Edouard Vannier, Alexander Poltorak
Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28611044/characterization-of-mk-4166-a-clinical-agonistic-antibody-that-targets-human-gitr-and-inhibits-the-generation-and-suppressive-effects-of-t-regulatory-cells
#13
Selvakumar Sukumar, Douglas C Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M Pinheiro, Venkataraman Sriram, Wendy J Bailey, Danuta Herzyk, Terrill K McClanahan, Aarron Willingham, Amy M Beebe, Svetlana Sadekova
GITR is a T cell co-stimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here we report the potential utility of MK-4166, a humanized GITR monoclonal antibody selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TILs)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28609844/an-overview-on-immunoregulatory-and-anti-inflammatory-properties-of-chrysin-and-flavonoids-substances
#14
REVIEW
Majid Zeinali, Seyed Abdolrahim Rezaee, Hossein Hosseinzadeh
Inflammation and the pro-inflammatory cytokines are associated with numerous chronic diseases. Studies suggest that flavonoids, plant polyphenolic compound derivatives from natural origin, have a wide range of putative biological activities. Similar to other flavonoids, chrysin (CH) by its anti-oxidative and anti-inflammatory effects is a potential prophylactic agent in immunopathological and physicochemical injuries. This is an overview on putative immunomodulatory activities of flavonoids and beneficial health effects of these substances particularly, CH in the immune system...
June 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28609144/therapeutic-benefit-of-mesenchymal-stem-cells-in-pregnant-rats-with-angiotensin-receptor-agonistic-autoantibody-induced-hypertension-implications-for-immunomodulation-and-cytoprotection
#15
Dan Zhang, Lihua Fu, Leilei Wang, Lin Lin, Lihong Yu, Lijun Zhang, Tao Shang
Immunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord-derived mesenchymal stem cells (HU-MSCs) for the treatment of angiotensin receptor agonistic autoantibody (AT1-AA)-induced hypertension during pregnancy. HU-MSCs were isolated, cultured, and labeled in vitro. AT1-AA and HU-MSCs were administered to pregnant rats...
June 13, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/28606988/recurrent-rhinovirus-infections-in-a-child-with-inherited-mda5-deficiency
#16
Ian T Lamborn, Huie Jing, Yu Zhang, Scott B Drutman, Jordan K Abbott, Shirin Munir, Sangeeta Bade, Heardley M Murdock, Celia P Santos, Linda G Brock, Evan Masutani, Emmanuel Y Fordjour, Joshua J McElwee, Jason D Hughes, Dave P Nichols, Aziz Belkadi, Andrew J Oler, Corinne S Happel, Helen F Matthews, Laurent Abel, Peter L Collins, Kanta Subbarao, Erwin W Gelfand, Michael J Ciancanelli, Jean-Laurent Casanova, Helen C Su
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs...
June 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28606052/targeting-the-tumor-microenvironment-by-intervention-in-interleukin-1-biology
#17
Elena Voronov, Ron N Apte
The importance of anti-tumor immunity in the outcome of cancer is now unequivocally established and recent achivements in the field have stimulated the development of new immunotherapeutical approaches. In invasive tumors, widespread inflammation promotes invasiveness and concomitantly also inhibits anti-tumor immune responses. We suggest that efficient tumor treatment should target both the malignant cells and the tumor microenvironment. Interleukin-1 (IL-1) is a pro-inflammatory as well as an immunostimulatory cytokine that is abundant in the tumor microenvironment...
June 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28603493/role-of-atypical-chemokine-receptors-in-microglial-activation-and-polarization
#18
REVIEW
Valentina Salvi, Francesca Sozio, Silvano Sozzani, Annalisa Del Prete
Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28599794/a-novel-combination-adjuvant-platform-for-human-and-animal-vaccines
#19
Ravendra Garg, Lorne Babiuk, Sylvia van Drunen Littel-van den Hurk, Volker Gerdts
Adjuvants are crucial components of many vaccines. They are used to improve the immunogenicity of vaccines with the aim of conferring long-term protection, to enhance the efficacy of vaccines in newborns, elderly or immunocompromised persons, and to reduce the amount of antigen or the number of doses required to elicit effective immunity. Novel combination adjuvants have been tested in both candidate animals and humans vaccines and have generated encouraging results. Recently, we developed a combination adjuvant platform (TriAdj) comprising of three components, namely a TLR agonist, either polyI:C or CpG oligodeoxynucleotides (ODN), host defense peptide and polyphosphazene...
June 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28596770/a-phase-1-human-immunodeficiency-virus-vaccine-trial-for-cross-profiling-the-kinetics-of-serum-and-mucosal-antibody-responses-to-cn54gp140-modulated-by-two-homologous-prime-boost-vaccine-regimens
#20
Sven Kratochvil, Paul F McKay, Jakub T Kopycinski, Cynthia Bishop, Peter John Hayes, Luke Muir, Christopher L Pinder, Deniz Cizmeci, Deborah King, Yoann Aldon, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent, Kathrin Held, Christof Geldmacher, Len Dally, Nelson S Santos, Tom Cole, Jill Gilmour, Sarah Fidler, Robin J Shattock
A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months...
2017: Frontiers in Immunology
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