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https://www.readbyqxmd.com/read/29769448/tlr-adjuvanted-nanoparticle-vaccines-differentially-influence-the-quality-and-longevity-of-responses-to-malaria-antigen-pfs25
#1
Elizabeth A Thompson, Sebastian Ols, Kazutoyo Miura, Kelly Rausch, David L Narum, Mats Spångberg, Michal Juraska, Ulrike Wille-Reece, Amy Weiner, Randall F Howard, Carole A Long, Patrick E Duffy, Lloyd Johnston, Conlin P O'Neil, Karin Loré
Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)-based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29760193/expression-of-the-atypical-chemokine-receptor-ackr4-identifies-a-novel-population-of-intestinal-submucosal-fibroblasts-that-preferentially-expresses-endothelial-cell-regulators
#2
Carolyn A Thomson, Serge A van de Pavert, Michelle Stakenborg, Evelien Labeeuw, Gianluca Matteoli, Allan McI Mowat, Robert J B Nibbs
Atypical chemokine receptors (ACKRs) are expressed by discrete populations of stromal cells at specific anatomical locations where they control leukocyte migration by scavenging or transporting chemokines. ACKR4 is an atypical receptor for CCL19, CCL21, and CCL25. In skin, ACKR4 plays indispensable roles in regulating CCR7-dependent APC migration, and there is a paucity of migratory APCs in the skin-draining lymph nodes of Ackr4 -deficient mice under steady-state and inflammatory conditions. This is caused by loss of ACKR4-mediated CCL19/21 scavenging by keratinocytes and lymphatic endothelial cells...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29747051/immune-modulation-of-two-batf3-paralogues-in-rainbow-trout-oncorhynchus-mykiss
#3
Jun Wang, Min Liu, Yang Wu, Sohye Yoon, Abdo Alnabulsi, Fuguo Liu, Clara Fernández-Álvarez, Tiehui Wang, Jason W Holland, Chris J Secombes, Jun Zou
Basic leucine zipper transcription factor ATF-like (BATF) -3 is a member of the activator protein 1 (AP‑1) family of transcription factors and is known to play a vital role in regulating differentiation of antigen-presenting cells in mammals. In this study, two BATF3 homologues (termed BATF3a and BATF3b) have been identified in rainbow trout (Oncorhynchus mykiss). Both genes were constitutively expressed in tissues, with particularly high levels of BATF3a in spleen, liver, pyloric caecae and head kidney. BATF3a was also more highly induced by PAMPs and cytokines in cultured cells, with type II IFN a particularly potent inducer...
May 7, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29717111/low-doses-of-lps-exacerbate-the-inflammatory-response-and-trigger-death-on-tlr3-primed-human-monocytes
#4
Marta Monguió-Tortajada, Marcella Franquesa, Maria-Rosa Sarrias, Francesc E Borràs
TLR sensing of pathogens triggers monocyte activation to initiate the host innate immune response to infection. Monocytes can dynamically adapt to different TLR agonists inducing different patterns of inflammatory response, and the sequence of exposure to TLRs can dramatically modulate cell activation. Understanding the interactions between TLR signalling that lead to synergy, priming and tolerance to TLR agonists may help explain how prior infections and inflammatory conditioning can regulate the innate immune response to subsequent infections...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29715306/pentoxifylline-dexamethasone-and-azithromycin-demonstrate-distinct-age-dependent-and-synergistic-inhibition-of-tlr-and-inflammasome-mediated-cytokine-production-in-human-newborn-and-adult-blood-in-vitro
#5
Esther M Speer, David J Dowling, Jianjin Xu, Lukasz S Ozog, Jaime A Mathew, Avinash Chander, Donglei Yin, Ofer Levy
INTRODUCTION: Neonatal inflammation, mediated in part through Toll-like receptor (TLR) and inflammasome signaling, contributes to adverse outcomes including organ injury. Pentoxifylline (PTX), a phosphodiesterase inhibitor which potently suppresses cytokine production in newborn cord blood, is a candidate neonatal anti-inflammatory agent. We hypothesized that combinations of PTX with other anti-inflammatory agents, the steroid dexamethasone (DEX) or the macrolide azithromycin (AZI), may exert broader, more profound and/or synergistic anti-inflammatory activity towards neonatal TLR- and inflammasome-mediated cytokine production...
2018: PloS One
https://www.readbyqxmd.com/read/29695694/-maturation-and-antigen-loading-protocols-influence-activity-of-anticancer-dendritic-cells
#6
Zh K Nazarkina, A Zajakina, P P Laktionov
The practical use of dendritic cell-based vaccines in anticancer therapy is limited by a lack of standards for dendritic cell (DC) generation, as well as standard procedures for controlling their activation and the technique of DC loading with nucleic acids encoding tumor antigens. Analyzing the currently available data, the most promising cocktails for DC maturation were selected and a comparative study of the cocktails and time of maturation on the capacity of DC to activate T-cell immune response has been performed...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29678225/synergistic-effect-of-co-stimulation-of-membrane-and-endosomal-tlrs-on-chicken-innate-immune-responses
#7
Sungwon Kim, Pete Kaiser, Dominika Borowska, Lonneke Vervelde
Toll-like receptor (TLR) ligands (TLR-Ls) are critical activators of immunity and are successfully being developed as vaccine adjuvants in both mammals and birds. In this study, we investigated the synergistic effect of co-stimulation of membrane and endosomal TLRs on the innate immune responses using chicken bone marrow-derived macrophages (BMMs), and studied the effect of age on the induction of innate responses. BMMs from 1 and 4-week-old birds were stimulated with Pam3Cys-SK4 (PCSK; TLR2), synthetic monophosphoryl lipid A (MPLA), Di[3-deoxy-d-manno-octulosonyl]-lipid A ammonium salt (KLA; TLR4), Gardiquimod, Resiquimod (R848; TLR7), CpG class B and C (TLR21)...
May 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29673285/tlr-agonist-combinations-that-stimulate-th-type-i-polarizing-responses-from-human-neonates
#8
Naveen Surendran, Andrea Simmons, Michael E Pichichero
Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29665497/the-effects-of-resiquimod-in-an-ovalbumin-induced-allergic-rhinitis-model
#9
Shenhong Qu, Taijie Qin, Min Li, Shaojie Zhang, Linsong Ye, Jiazhang Wei, Hua Fan, Baiwen Chen
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29619028/mapk-phosphatase-1-deficiency-exacerbates-the-severity-of-imiquimod-induced-psoriasiform-skin-disease
#10
Weiheng Zhao, Shuxiu Xiao, Hongjin Li, Tingting Zheng, Jian Huang, Ran Hu, Baohua Zhang, Xinguang Liu, Gonghua Huang
Persistent activation of mitogen-activated protein kinase (MAPK) is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1) is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ)-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1-/- ) mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29569859/toll-like-receptor-7-8-activation-exacerbates-murine-experimental-autoimmune-myositis
#11
Clara Sciorati, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Dana P Ascherman, Angelo A Manfredi, Patrizia Rovere-Querini
OBJECTIVE: TLR-7/8 and Interferon (IFN)-induced genes are expressed in patients with inflammatory idiopathic myositis. Here we investigated whether their activation influences the natural history of the disease. METHODS: Experimental autoimmune myositis (EAM) was induced by injection of the amino-terminal portion of the murine Histydil t-RNA synthetase (HisRS). Disease was compared in the presence or the absence of the TLR-7/8 agonist R848 in wild-type mice and in mice that fail to express the IFNαβ receptor (IFNαβR null)...
March 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29545793/src-family-kinases-regulate-interferon-regulatory-factor-1-k63-ubiquitination-following-activation-by-tlr7-8-vaccine-adjuvant-in-human-monocytes-and-b-cells
#12
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29515583/k63-linked-polyubiquitination-on-traf6-regulates-lps-mediated-mapk-activation-cytokine-production-and-bacterial-clearance-in-toll-like-receptor-7-8-primed-murine-macrophages
#13
Jaya Talreja, Lobelia Samavati
Post viral infection bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. Despite much efforts put into the discovery of mechanisms of post viral-bacterial infections and their complications in recent years, the molecular mechanisms underlying the increased susceptibility to bacterial infection remain poorly understood. In this study, we focused on the pathways regulating immune responses in murine macrophages and modeled post viral-bacterial infections through pretreatment of bone marrow-derived macrophages (BMDMs) with a toll-like receptor (TLR) 7/8 ligand (R848) and subsequent challenge with TLR2/4 agonists to mimic bacterial infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456540/kallikrein-kinin-system-suppresses-type-i-interferon-responses-a-novel-pathway-of-interferon-regulation
#14
Alecia Seliga, Michael Hweemoon Lee, Nicole C Fernandes, Viviana Zuluaga-Ramirez, Marta Didukh, Yuri Persidsky, Raghava Potula, Stefania Gallucci, Uma Sriram
The Kallikrein-Kinin System (KKS), comprised of kallikreins (klks), bradykinins (BKs) angiotensin-converting enzyme (ACE), and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand), R848 (TLR7 ligand), or recombinant IFN-α to induce interferon-stimulated genes (ISGs) and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein), or captopril (an ACE inhibitor)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29432791/functional-signalling-and-transcriptional-differences-of-three-distinct-type-i-ifns-in-a-perciform-fish-the-mandarin-fish-siniperca-chuatsi
#15
Zubair Ahmed Laghari, Shan Nan Chen, Li Li, Bei Huang, Zhen Gan, Ying Zhou, Hui Jun Huo, Jing Hou, Pin Nie
Teleost fish are unique in having type I and type II interferons (IFNs) only, and the type I IFNs are classified into Group one and Group two based on the presence of two or four cysteines respectively, and are further classified into seven subgroups. In the present study, three distinct type I IFNs, IFNc, IFNd and IFNh, have been identified in the genome sequences of a perciform fish, the mandarin fish Siniperca chuatsi. These IFNs are induced following the stimulation of Polyinosinic polycytidylic acid (poly(I:C)) and Resiquimod (R848) either in vivo or in vitro...
July 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29415180/neonatal-bcg-vaccination-influences-cytokine-responses-to-toll-like-receptor-ligands-and-heterologous-antigens
#16
B Freyne, S Donath, S Germano, K Gardiner, D Casalaz, R M Robins-Browne, N Amenyogbe, N L Messina, M G Netea, K L Flanagan, T Kollmann, N Curtis
Background: Bacille Calmette-Guérin (BCG) vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain but long-term modulation of the innate immune response (trained immunity) may be involved. Methods: Whole blood, collected 7 days post randomisation from 212 neonates enrolled in a randomised trial of neonatal BCG vaccination, was stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses...
February 3, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29409680/routing-dependent-immune-responses-after-experimental-r848-adjuvated-vaccination
#17
Susan van Aalst, Manon A A Jansen, Irene S Ludwig, Ruurd van der Zee, Willem van Eden, Femke Broere
Most traditional vaccines are administered via the intramuscular route. Other routes of administration however, can induce equal or improved protective memory responses and might provide practical advantages such as needle-free immunization, dose sparing and induction of tissue-specific (mucosal) immunity. Here we explored the differences in immunological outcome after immunization with model antigens via two promising immunization routes (intradermal and intranasal) with or without the experimental adjuvant and TLR7/8-agonist R848...
March 7, 2018: Vaccine
https://www.readbyqxmd.com/read/29399392/pro-inflammatory-allogeneic-dcs-promote-activation-of-bystander-immune-cells-and-thereby-license-antigen-specific-t-cell-responses
#18
Grammatiki Fotaki, Chuan Jin, Mohanraj Ramachandran, Iliana Kyriaki Kerzeli, Alex Karlsson-Parra, Di Yu, Magnus Essand
Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29398273/the-choice-of-linker-for-conjugating-r848-to-inactivated-influenza-virus-determines-the-stimulatory-capacity-for-innate-immune-cells
#19
Marlena M Westcott, Elene A Clemens, Beth C Holbrook, S Bruce King, Martha A Alexander-Miller
Inactivated influenza vaccines are not approved for use in infants less than 6 months of age due to poor immunogenicity in that population. While the live attenuated influenza vaccine has the potential to be more immunogenic, it is not an option for infants and other vulnerable populations, including the elderly and immunocompromised individuals due to safety concerns. In an effort to improve the immunogenicity of the inactivated vaccine for use in vulnerable populations, we have used an approach of chemically crosslinking the Toll-like receptor (TLR) 7/8 agonist R848 directly to virus particles...
February 21, 2018: Vaccine
https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#20
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
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