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https://www.readbyqxmd.com/read/28329288/tlr-agonists-can-they-exact-a-toll-on-hiv-persistence
#1
Joshua C Cyktor, John W Mellors
No abstract text is available yet for this article.
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28325863/pharmacological-targeting-of-plasmin-prevents-lethality-in-a-murine-model-of-macrophage-activation-syndrome
#2
Hiroshi Shimazu, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Douaa Dhahri, Salita Eiamboonsert, Yasunori Ota, Haruo Onoda, Yuko Tsuda, Yoshio Okada, Hiromitsu Nakauchi, Beate Heissig, Koichi Hattori
Macrophage activation syndrome (MAS) is a life-threatening disorder characterized by a cytokine storm and multiorgan dysfunction due to excessive immune activation. Although abnormalities of coagulation and fibrinolysis are major components of MAS, the role of the fibrinolytic system and its key player, plasmin, in the development of MAS remains to be solved. We established a murine model of fulminant MAS by repeated injections of Toll-like receptor-9 (TLR-9) agonist and D-galactosamine (DG) in immunocompetent mice...
March 21, 2017: Blood
https://www.readbyqxmd.com/read/28323387/induction-of-tumor-regression-by-intratumoral-sting-agonists-combined-with-anti-programmed-death-l1-blocking-antibody-in-a-preclinical-squamous-cell-carcinoma-model
#3
Shekhar K Gadkaree, Juan Fu, Rupashree Sen, Michael J Korrer, Clint Allen, Young J Kim
BACKGROUND: Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. METHODS: We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control)...
March 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28322156/recent-findings-on-the-application-of-toll-like-receptors-agonists-in-cancer-therapy
#4
Martina Mikulandra, Jasminka Pavelic, Tanja Matijevic Glavan
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs are Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28303762/tlr9-based-immunotherapy-for-the-treatment-of-allergic-diseases
#5
Shokrollah Farrokhi, Narjes Abbasirad, Ali Movahed, Hossein Ali Khazaei, Masoud Pishjoo, Nima Rezaei
Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28299776/toll-like-receptors-elicit-different-recruitment-kinetics-of-monocytes-and-neutrophils-in-mouse-acute-inflammation
#6
Beat A Imhof, Stephane Jemelin, Yalin Emre
Leukocyte recruitment is an important process in combatting pathogens. The largest class of circulating leukocytes are neutrophils, which rapidly invade inflamed tissue, followed by inflammatory Ly6C(+) monocytes. Ly6C(low) monocytes patrol the endothelial wall routinely in the steady state. We recently reported early luminal recruitment of Ly6C(low) monocytes, which preceded and orchestrated neutrophil arrival and extravasation in response to TLR7/8-mediated vascular inflammation. Here we dissected the kinetics of recruitment of monocytes and neutrophils and examined the dynamics of Ly6C(low) monocytes in response to several other Toll-like receptor (TLR) agonists, using intravital confocal microscopy...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28284594/orally-administered-live-attenuated-salmonella-typhimurium-protects-mice-against-lethal-infection-with-h1n1-influenza-virus
#7
Nitin Machindra Kamble, Irshad Ahmed Hajam, John Hwa Lee
Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-fi-rsv-enhanced-airway-hyperresponsiveness-and-inflammation-through-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#8
Lei Zhang, Hongyong Li, Yan Hai, Wei Yin, Wenjian Li, Boyang Zheng, Xiaomin Du, Na Li, Zhengzheng Zhang, Yuqing Deng, Ruihong Zeng, Lin Wei
Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross-talk between TLR and Notch signaling pathways results in fine tuning of TLR-triggered innate inflammatory responses...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28274989/nadph-oxidase-nox2-mediates-tlr2-6-dependent-release-of-gm-csf-from-endothelial-cells
#9
Jutta Schuett, Harald Schuett, Raghav Oberoi, Ann-Kathrin Koch, Silke Pretzer, Maren Luchtefeld, Bernhard Schieffer, Karsten Grote
NADPH oxidase-generated reactive oxygen species (ROS) from immune cells are well known to be important for pathogen killing in response to TLR ligands. Here, we investigated a new aspect of NADPH oxidase in the TLR2/6-induced release of the immunologically relevant GM-CSF by endothelial cells. Stimulation of human endothelial cells with TLR2/6 agonist, MALP-2 (macrophage-activating lipopeptide of 2 kDa), induced NADPH oxidase activation and ROS formation. Inhibition by ROS scavengers and NADPH oxidase inhibitors blocked MALP-2-induced GM-CSF release...
March 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28273337/ethanol-tlr3-and-tlr4-agonists-have-unique-innate-immune-responses-in-neuron-like-sh-sy5y-and-microglia-like-bv2
#10
Colleen J Lawrimore, Fulton T Crews
Ethanol (EtOH) consumption leads to an increase of proinflammatory signaling via activation of toll-like receptors (TLRs) such as TLR3 and TLR4 that leads to kinase activation (ERK1/2, p38, TBK1), transcription factor activation (NFκB, IRF3) and increased transcription of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6. This immune signaling cascade is thought to play a role in neurodegeneration and alcohol use disorders. While microglia are considered to be the primary macrophage in brain, it is unclear what if any role neurons play in ethanol-induced proinflammatory signaling METHODS: Microglia-like BV2 and retinoic acid differentiated neuron-like SH-SY5Y were treated with TLR3 agonist Poly(I:C), TLR4 agonist LPS, or EtOH for 10 or 30 minutes to examine proinflammatory immune signaling kinase and transcription factor activation using western blot, and for 24 hours to examine induction of proinflammatory gene mRNA using RT-PCR RESULTS: In BV2, both LPS and Poly(I:C) increased p-ERK1/2, p-p38, and p-NFκB by 30 minutes, whereas EtOH decreased p-ERK1/2 and increased p-IRF3...
March 8, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28270814/the-novel-toll-like-receptor-2-agonist-sup3-enhances-antigen-presentation-and-t-cell-activation-by-dendritic-cells
#11
Xueheng Guo, Ning Wu, Yingli Shang, Xin Liu, Tao Wu, Yifan Zhou, Xin Liu, Jiaoyan Huang, Xuebin Liao, Li Wu
Dendritic cells (DCs) are highly specialized antigen-presenting cells that play crucial roles in innate and adaptive immunity. Previous studies suggested that Toll-like receptor (TLR) agonists could be used as potential adjuvants, as activation of TLRs can boost DC-induced immune responses. TLR2 agonists have been shown to enhance DC-mediated immune responses. However, classical TLR2 agonists such as Pam3CSK4 are not stable enough in vivo, which limits their clinical applications. In this study, a novel structurally stable TLR2 agonist named SUP3 was designed...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28264968/tim-3-is-a-marker-of-plasmacytoid-dendritic-cell-dysfunction-during-hiv-infection-and-is-associated-with-the-recruitment-of-irf7-and-p85-into-lysosomes-and-with-the-submembrane-displacement-of-tlr9
#12
Jordan Ari Schwartz, Kiera L Clayton, Shariq Mujib, Hongliang Zhang, A K M Nur-Ur Rahman, Jun Liu, Feng Yun Yue, Erika Benko, Colin Kovacs, Mario A Ostrowski
In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28263189/cd11b-activation-suppresses-tlr-dependent-inflammation-and-autoimmunity-in-systemic-lupus-erythematosus
#13
Mohd Hafeez Faridi, Samia Q Khan, Wenpu Zhao, Ha Won Lee, Mehmet M Altintas, Kun Zhang, Vinay Kumar, Andrew R Armstrong, Carmelo Carmona-Rivera, Jessica M Dorschner, Abigail M Schnaith, Xiaobo Li, Yogita Ghodke-Puranik, Erica Moore, Monica Purmalek, Jorge Irizarry-Caro, Tingting Zhang, Rachael Day, Darren Stoub, Victoria Hoffmann, Shehryar Jehangir Khaliqdina, Prachal Bhargava, Ana M Santander, Marta Torroella-Kouri, Biju Issac, David J Cimbaluk, Andrew Zloza, Rajeev Prabhakar, Shashank Deep, Meenakshi Jolly, Kwi Hye Koh, Jonathan S Reichner, Elizabeth M Bradshaw, JianFeng Chen, Luis F Moita, Peter S Yuen, Wanxia Li Tsai, Bhupinder Singh, Jochen Reiser, Swapan K Nath, Timothy B Niewold, Roberto I Vazquez-Padron, Mariana J Kaplan, Vineet Gupta
Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury...
March 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28257481/toll-like-receptor-2-activation-and-serum-amyloid-a-regulate-smooth-muscle-cell-extracellular-matrix
#14
Stephanie E Seidl, Lawrence G Pessolano, Christopher A Bishop, Michael Best, Celeste B Rich, Phillip J Stone, Barbara M Schreiber
Smooth muscle cells contribute to extracellular matrix remodeling during atherogenesis. De-differentiated, synthetic smooth muscle cells are involved in processes of migration, proliferation and changes in expression of extracellular matrix components, all of which contribute to loss of homeostasis accompanying atherogenesis. Elevated levels of acute phase proteins, including serum amyloid A (SAA), are associated with an increased risk for atherosclerosis. Although infection with periodontal and respiratory pathogens via activation of inflammatory cell Toll-like receptor (TLR)2 has been linked to vascular disease, little is known about smooth muscle cell TLR2 in atherosclerosis...
2017: PloS One
https://www.readbyqxmd.com/read/28250157/il-6-production-by-tlr-activated-apc-broadly-enhances-aged-cognate-cd4-helper-and-b-cell-antibody-responses-in-vivo
#15
Vinayak Brahmakshatriya, Yi Kuang, Priyadharshini Devarajan, Jingya Xia, Wenliang Zhang, Allen Minh Vong, Susan L Swain
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28245863/epstein-barr-virus-lytic-infection-promotes-activation-of-toll-like-receptor-8-innate-immune-response-in-systemic-sclerosis-monocytes
#16
Antonella Farina, Giovanna Peruzzi, Valentina Lacconi, Stefania Lenna, Silvia Quarta, Edoardo Rosato, Anna Rita Vestri, Michael York, David H Dreyfus, Alberto Faggioni, Stefania Morrone, Maria Trojanowska, G Alessandra Farina
BACKGROUND: Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion...
February 28, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28245781/endogenous-and-exogenous-natural-adjuvants-for-vaccine-development
#17
Azam Bolhassani, Somayeh Talebi, Ali Anvar
Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds (e...
February 28, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28242239/role-of-toll-like-receptor-4-in-drug-drug-interaction-between-paclitaxel-and-irinotecan-in-vitro
#18
Pankajini Mallick, Sumit Basu, Bhagavtula Moorthy, Romi Ghose
The bacterial receptor, Toll-like receptor (TLR) 4 mediates inflammatory responses and has been linked to a broad array of diseases. TLR4 agonists are being explored as potential treatments for cancer and other diseases. We have previously shown that activation of TLR4 by lipopolysaccharide (LPS) leads to down-regulation of drug metabolizing enzymes/transporters (DMETs), and altered pharmacokinetics/pharmacodynamics (PK/PD) of drugs. These changes can increase the risk of drug-drug interactions (DDIs) in patients on multiple medications...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28237711/pharmacological-inhibition-of-faah-modulates-tlr-induced-neuroinflammation-but-not-sickness-behaviour-an-effect-partially-mediated-by-central-trpv1
#19
Rebecca J Henry, Daniel M Kerr, Lisa E Flannery, Marykate Killilea, Edel M Hughes, Louise Corcoran, David P Finn, Michelle Roche
Aberrant activation of toll-like receptors (TLRs), key components of the innate immune system, has been proposed to underlie and exacerbate a range of central nervous system disorders. Increasing evidence supports a role for the endocannabinoid system in modulating inflammatory responses including those mediated by TLRs, and thus this system may provide an important treatment target for neuroinflammatory disorders. However, the effect of modulating endocannabinoid tone on TLR-induced neuroinflammation in vivo and associated behavioural changes is largely unknown...
February 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28235773/tlr10-suppresses-the-activation-and-differentiation-of-monocytes-with-effects-on-dc-mediated-adaptive-immune-responses
#20
Nicholas J Hess, Christopher Felicelli, Jennifer Grage, Richard I Tapping
TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation...
February 24, 2017: Journal of Leukocyte Biology
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