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https://www.readbyqxmd.com/read/29138398/characterization-of-macrophages-from-schizophrenia-patients
#1
Paul R Ormel, Hans C van Mierlo, Manja Litjens, Miriam E van Strien, Elly M Hol, René S Kahn, Lot D de Witte
Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. It has therefore been hypothesized that aberrant functioning of these myeloid immune cells is involved in SCZ pathogenesis. Until now cellular research into the role of myeloid cells in SCZ has been limited to monocytes and functional assays are lacking...
November 14, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29129789/dual-ph-responsive-multifunctional-nanoparticles-for-targeted-treatment-of-breast-cancer-by-combining-immunotherapy-and-chemotherapy
#2
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
November 9, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29097235/unc93b1-is-essential-for-cytokine-activation-of-five-pamps-in-the-orange-spotted-grouper-epinephelus-coioides
#3
Yaosi Liang, Yu Wang, Liangge He, Jianan He, Wan Peng, Libin Zhou, Yong Zhang, Haifa Zhang, Herong Shi, Haoran Lin, Danqi Lu
Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 (unc93b1), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco...
October 31, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29079801/development-of-a-curative-therapeutic-vaccine-theravac-for-the-treatment-of-large-established-tumors
#4
Yingjie Nie, De Yang, Anna Trivett, Zhen Han, Haiyun Xin, Xin Chen, Joost J Oppenheim
Harnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053867/molecular-cloning-and-functional-analysis-of-peafowl-pavo-cristatus-toll-like-receptor-7
#5
H Song, M Zhang, W Gao, L Wu, G Li
In order to clone the peafowl (Pavo cristatus) Toll-like receptor 7 (TLR7) gene and study its biological function, the peafowl TLR7 coding sequences (CDS) were amplified by PCR of cDNA from the whole spleen of peafowl. The full-length sequence of the peafowl TLR7 gene CDS is 3,141 bp and encodes a 1,046-amino acid protein with a classic TLR composition of 16 leucine-rich repeats (LRR). Insertions of amino acids were found at position 15 of LRR2, LRR5, LRR7, LRR9, LRR11, LRR12, LRR14, and LRR15; and position 10 of LRR11...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/28967521/adjuvanting-an-inactivated-influenza-vaccine-with-conjugated-r848-improves-the-level-of-antibody-present-at-6months-in-a-nonhuman-primate-neonate-model
#6
Beth C Holbrook, Ralph B D'Agostino, S Tyler Aycock, Matthew J Jorgensen, Mallinath B Hadimani, S Bruce King, Martha A Alexander-Miller
Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28963929/evaluation-of-the-adjuvant-effect-of-agonists-of-toll-like-receptor-4-and-7-8-in-a-vaccine-against-leishmaniasis-in-balb-c-mice
#7
Mosayeb Rostamian, Hamid M Niknam
There is no effective vaccine against human leishmaniasis. Achieving successful vaccines seems to need powerful adjuvants. Separate or combined use of toll like receptor (TLR) agonists as adjuvant is a promising approach in Leishmania vaccine research. In present study, we evaluated adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice. Mice were vaccinated three times by SLA with separate or combined TLR7/8 and TLR4 agonists and were then challenged by Leishmania major...
November 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28958808/human-innate-responses-and-adjuvant-activity-of-tlr-ligands-in-vivo-in-mice-reconstituted-with-a-human-immune-system
#8
Liang Cheng, Zheng Zhang, Guangming Li, Feng Li, Li Wang, Liguo Zhang, Sandra M Zurawski, Gerard Zurawski, Yves Levy, Lishan Su
TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28955328/co-delivery-of-dual-toll-like-receptor-agonists-and-antigen-in-poly-lactic-co-glycolic-acid-polyethylenimine-cationic-hybrid-nanoparticles-promote-efficient-in-vivo-immune-responses
#9
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28940186/an-r848-adjuvanted-influenza-vaccine-promotes-early-activation-of-b-cells-in-the-draining-lymph-node-of-nonhuman-primate-neonates
#10
Beth C Holbrook, S Tyler Aycock, Emily Machiele, Elene Clemens, Danielle Gries, Matthew J Jorgensen, Mallinath B Hadimani, S Bruce King, Martha A Alexander-Miller
Impaired immune responsiveness is a significant barrier to vaccination of neonates. By way of example, the low seroconversion observed following influenza vaccination has led to restriction of its use to infants over 6 months of age, leaving younger infants vulnerable to infection. Our previous studies using a nonhuman primate neonate model demonstrated that the immune response elicited following vaccination with inactivated influenza virus could be robustly increased by inclusion of the TLR agonist flagellin or R848, either delivered individually or in combination...
September 22, 2017: Immunology
https://www.readbyqxmd.com/read/28924041/irak4-kinase-activity-controls-toll-like-receptor-induced-inflammation-through-the-transcription-factor-irf5-in-primary-human-monocytes
#11
Leah Cushing, Aaron Winkler, Scott A Jelinsky, Katherine Lee, Wouter Korver, Rachael Hawtin, Vikram R Rao, Margaret Fleming, Lih-Ling Lin
Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate immune signaling by Toll-like receptors (TLRs), and loss of IRAK4 activity in mice and humans increases susceptibility to bacterial infections and causes defects in TLR and IL1 ligand sensing. However, the mechanism by which IRAK4 activity regulates the production of downstream inflammatory cytokines is unclear. Using transcriptomic and biochemical analyses of human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the activation of interferon regulatory factor 5 (IRF5), a transcription factor implicated in the pathogenesis of multiple autoimmune diseases...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28921509/baff-augments-iga2-and-il-10-production-by-tlr7-8-stimulated-total-peripheral-blood-b%C3%A2-cells
#12
Gerco den Hartog, Thijs L J van Osch, Martijn Vos, Ben Meijer, Huub F J Savelkoul, R J Joost van Neerven, Sylvia Brugman
Class-switching of B cells to IgA can be induced via both T-cell-dependent and T-cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T-cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection...
September 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28910320/differential-gene-expression-following-tlr-stimulation-in-rag1-mutant-zebrafish-tissues-and-morphological-descriptions-of-lymphocyte-like-cell-populations
#13
Preeti J Muire, Larry A Hanson, Robert Wills, Lora Petrie-Hanson
In the absence of lymphocytes, rag1-/- mutant zebrafish develop protective immunity to bacteria. In mammals, induction of protection by innate immunity can be mediated by macrophages or natural killer (NK) cells. To elucidate potential responsive cell populations, we morphologically characterized lymphocyte-like cells (LLCs) from liver, spleen and kidney hematopoietic tissues. In fish, these cells include NK cells and Non-specific cytotoxic cells (NCCs). We also evaluated the transcriptional expression response of select genes that are important indicators of NK and macrophage activation after exposure to specific TLR ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28881713/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#14
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878767/human-blood-cd1c-dendritic-cells-promote-th1-and-th17-effector-function-in-memory-cd4-t-cells
#15
Ingrid M Leal Rojas, Wai-Hong Mok, Frances E Pearson, Yoshihito Minoda, Tony J Kenna, Ross T Barnard, Kristen J Radford
Dendritic cells (DC) initiate the differentiation of CD4(+) helper T cells into effector cells including Th1 and Th17 responses that play an important role in inflammation and autoimmune disease pathogenesis. In mice, Th1 and Th17 responses are regulated by different conventional (c) DC subsets, with cDC1 being the main producers of IL-12p70 and inducers of Th1 responses, while cDC2 produce IL-23 to promote Th17 responses. The role that human DC subsets play in memory CD4(+) T cell activation is not known. This study investigated production of Th1 promoting cytokine IL-12p70, and Th17 promoting cytokines, IL-1β, IL-6, and IL-23, by human blood monocytes, CD1c(+) DC, CD141(+) DC, and plasmacytoid DC and examined their ability to induce Th1 and Th17 responses in memory CD4(+) T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28835457/neuroendocrine-modulation-of-il-27-in-macrophages
#16
Julian Roewe, Maximilian Higer, Dennis R Riehl, Adrian Gericke, Markus P Radsak, Markus Bosmann
Heterodimeric IL-27 (p28/EBV-induced gene 3) is an important member of the IL-6/IL-12 cytokine family. IL-27 is predominantly synthesized by mononuclear phagocytes and exerts immunoregulatory functional activities on lymphocytic and nonlymphocytic cells during infection, autoimmunity or neoplasms. There is a great body of evidence on the bidirectional interplay between the autonomic nervous system and immune responses during inflammatory disorders, but so far IL-27 has not been defined as a part of these multifaceted neuroendocrine networks...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28826648/the-synergistic-effects-of-combining-tlr-ligand-based-adjuvants-on-the-cytokine-response-are-dependent-upon-p38-jnk-signalling
#17
Lucia Fischetti, Ziyun Zhong, Christopher L Pinder, John S Tregoning, Robin J Shattock
Toll like receptor (TLR) ligands are important adjuvant candidates, causing antigen presenting cells to release inflammatory mediators, leading to the recruitment and activation of other leukocytes. The aim of this study was to define the response of human blood derived dendritic cells and macrophages to three TLR ligands acting singly or in combination, Poly I:C (TLR3), GLA (TLR4) and R848 (TLR7/8). Combinations of TLR agonists have been shown to have a synergistic effect on individual cytokines, here we look at the global inflammatory response measuring both cytokines and chemokines...
August 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28808017/antitumor-effect-of-batf2-through-il-12-p40-up-regulation-in-tumor-associated-macrophages
#18
Hisashi Kanemaru, Fumihiro Yamane, Kiyoharu Fukushima, Takanori Matsuki, Takahiro Kawasaki, Isao Ebina, Kanako Kuniyoshi, Hiroki Tanaka, Kenta Maruyama, Kazuhiko Maeda, Takashi Satoh, Shizuo Akira
The development of effective treatments against cancers is urgently needed, and the accumulation of CD8(+) T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40(+) macrophages and activated CD8(+) T cells within the tumors of Batf2(-/-) mice compared with WT mice...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28783457/platelets-modulate-innate-immune-response-against-human-respiratory-syncytial-virus-in-vitro
#19
Vesla I Kullaya, Quirijn de Mast, Andre van der Ven, Hicham elMoussaoui, Gibson Kibiki, Elles Simonetti, Marien I de Jonge, Gerben Ferwerda
Detection of respiratory syncytial virus (RSV) in blood, including mononuclear leukocytes and organs other than the lung, suggests that RSV disseminates outside the respiratory tract. In this study, the role of platelets in host defense against RSV was explored using an in vitro model. Platelets, also produced in the lungs, are increasingly recognized as an important part of host immune responses and may therefore play a role in modulating lung infections and clearing RSV viremia. In human peripheral blood mononuclear cells (PBMCs), platelets significantly reduced RSV infection of monocytes, monocyte activation, and interferon (IFN)α/γ production...
October 2017: Viral Immunology
https://www.readbyqxmd.com/read/28743833/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#20
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
July 18, 2017: Oncotarget
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