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https://www.readbyqxmd.com/read/29456540/kallikrein-kinin-system-suppresses-type-i-interferon-responses-a-novel-pathway-of-interferon-regulation
#1
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/29452403/mechanisms-controlling-nucleic-acid-sensing-toll-like-receptors
#2
Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu, Shin-Ichiroh Saitoh, Ryutaro Fukui, Yusuke Murakami
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization...
February 14, 2018: International Immunology
https://www.readbyqxmd.com/read/29448955/analysis-of-the-genetic-diversity-and-mrna-expression-level-in-porcine-reproductive-and-respiratory-syndrome-virus-vaccinated-pigs-that-developed-short-or-long-viremias-after-challenge
#3
Martí Cortey, Gaston Arocena, Tahar Ait-Ali, Anna Vidal, Yanli Li, Gerard Martín-Valls, Alison D Wilson, Allan L Archibald, Enric Mateu, Laila Darwich
Porcine reproductive and respiratory syndrome virus (PRRSv) infection alters the host's cellular and humoral immune response. Immunity against PRRSv is multigenic and vary between individuals. The aim of the present study was to compare several genes that encode for molecules involved in the immune response between two groups of vaccinated pigs that experienced short or long viremic periods after PRRSv challenge. These analyses include the sequencing of four SLA Class I, two Class II allele groups, and CD163, plus the analysis by quantitative realtime qRT-PCR of the constitutive expression of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA and other molecules in peripheral blood mononuclear cells...
February 15, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29448098/differences-in-tlr7-8-activation-between-monocytes-and-macrophages
#4
Hock-Liew Eng, Yuan-Ying Hsu, Tsun-Mei Lin
The recognition of single-stranded RNA by TLR7/8 leads to the production of NF-κB-mediated cytokines and type I IFNs. However, the role of TLR7/8 activation in monocytes and macrophages is still unclear. The aim of this study was to investigate the differences in the activation of TLR7/8 between these two cell types. Microarray analysis, qRT-PCR and flow cytometry were used to analyse TLR7/8 signalling pathways in monocytes and macrophages after stimulation with agonists. Our data indicated that TLR8 agonists activated the NF-κB- and IRF-mediated pathways in THP-1 cells, whereas TLR7 agonists did not...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29445364/non-specific-effect-of-vaccines-immediate-protection-against-respiratory-syncytial-virus-infection-by-a-live-attenuated-influenza-vaccine
#5
Young J Lee, Jeong Y Lee, Yo H Jang, Sang-Uk Seo, Jun Chang, Baik L Seong
The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29434596/insight-into-phosphatidylinositol-dependent-membrane-localization-of-the-innate-immune-adaptor-protein-toll-interleukin-1-receptor-domain-containing-adaptor-protein
#6
Mahesh Chandra Patra, Sangdun Choi
The toll/interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP) plays an important role in the toll-like receptor (TLR) 2, TLR4, TLR7, and TLR9 signaling pathways. TIRAP anchors to phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) on the plasma membrane and PI (3,4,5)-trisphosphate (PIP3) on the endosomal membrane and assists in recruitment of the myeloid differentiation primary response 88 protein to activated TLRs. To date, the structure and mechanism of TIRAP's membrane association are only partially understood...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29430014/autoimmunity-tlr7-evades-silencing-in-human-immune-cells
#7
Jack M Heintze
No abstract text is available yet for this article.
February 12, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29429903/increased-infiltration-of-cd11-c-cd123-dendritic-cell-subsets-and-upregulation-of-tlr-ifn-%C3%AE-signaling-participate-in-pathogenesis-of-oral-lichen-planus
#8
Yufeng Wang, Shu Shang, Qianqian Sun, Junjun Chen, Guanhuan Du, Hong Nie, Xiaozhe Han, Guoyao Tang
OBJECTIVE: Investigation of dendritic cell (DC) subsets and expression patterns of Toll-like receptors (TLRs) was conducted to understand the pathogenesis in oral lichen planus (OLP). STUDY DESIGN: Blood, OLP lesion, and control samples were collected. Four DC subsets (CD11c + CD123 - myeloid DC1 [mDC1], CD141 + mDC2, CD11c - CD123 + plasmacytoid DC [pDC], and CD1a + CD207 + Langerhans cells [LC]) were investigated via flow cytometry (FCM) and immunohistochemical staining...
December 18, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29427996/respiratory-syncytial-virus-prolifically-infects-n2a-neuronal-cells-leading-to-tlr4-and-nucleolin-protein-modulations-and-rsv-f-protein-co-localization-with-tlr4-and-nucleolin
#9
Xiaoling Yuan, Tao Hu, Hanwen He, Huan Qiu, Xuan Wu, Jingxian Chen, Minmin Wang, Cheng Chen, Shenghai Huang
BACKGROUND: Respiratory syncytial virus (RSV) infects the central nervous system, resulting in neurological symptoms. However, the precise underlying pathogenic mechanisms have not been elucidated. In the present study, the infectivity of RSV on N2a neuronal cells and the possible roles of Toll-like receptor 4 (TLR4) and nucleolin (C23) during RSV infection were investigated. METHODS: We compared two experimental groups (infected and non-infected) and monitored the RSV viral titers in the culture supernatant by a viral plaque assay...
February 10, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29425831/gs-9620-inhibits-enterovirus-71-replication-mainly-through-the-nf-%C3%AE%C2%BAb-and-pi3k-akt-signaling-pathways
#10
Qian Zhang, Binbin Zhao, Xin Chen, Nan Song, Jing Wu, Guangchao Li, Pin Yu, Yunlin Han, Jiangning Liu, Chuan Qin
Human enterovirus 71 (EV71) is the second most common cause of hand, foot, and mouth disease (HFMD), which can occur as a severe epidemic especially among children under 5-years old. New and improved treatment strategies to control EV71 infection are therefore urgently required. The heterocyclic compound GS-9620, a potent and selective agonist of Toll-like receptor 7 (TLR7), has been reported to activate plasmacytoid dendritic cells (pDCs), and suppress HBV as well as HIV replication. In this study, we indicated that GS-9620 also could inhibit EV71 replication in the mouse model of EV71 infection...
February 6, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29423077/integrating-the-dysregulated-inflammasome-based-molecular-functionome-in-the-malignant-transformation-of-endometriosis-associated-ovarian-carcinoma
#11
Chia-Ming Chang, Mong-Lien Wang, Kai-Hsi Lu, Yi-Ping Yang, Chi-Mou Juang, Peng-Hui Wang, Ren-Jun Hsu, Mu-Hsien Yu, Cheng-Chang Chang
The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421216/the-preparation-and-physico-chemical-characterization-of-aluminum-hydroxide-tlr7a-a-novel-vaccine-adjuvant-comprising-a-small-molecule-adsorbed-to-aluminum-hydroxide
#12
Padma Malyala, Donatello Laera, Simona Cianetti, Simone Bufali, Marianna Aggravi, Elvira Ianni, Casey Judge, Gillis Otten, Manmohan Singh, Derek T O' Hagan
Adjuvants are necessary to enable vaccine development against a significant number of challenging pathogens for which effective vaccines are not available [1]. We engineered a novel small-molecule immune potentiator (SMIP), a benzonaphthyridine agonist targeting toll-like receptor 7 (TLR7), as a vaccine adjuvant. TLR7 agonist (TLR7a) was engineered to be adsorbed onto aluminum hydroxide (AlOH), and the resulting AlOH/TLR7a was evaluated as a vaccine adjuvant [2-6]. AlOH/TLR7a exploits the flexibility of AlOH formulations, has an application in many vaccine candidates, and induced good efficacy and safety profiles against all tested antigens (bacterial- and viral-derived protein antigens, toxoids, glycoconjugates, etc...
February 5, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29415180/neonatal-bcg-vaccination-influences-cytokine-responses-to-toll-like-receptor-ligands-and-heterologous-antigens
#13
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
#14
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...
February 3, 2018: Vaccine
https://www.readbyqxmd.com/read/29408631/intracellular-tlr7-is-activated-in-human-oligodendrocytes-in-response-to-borrelia-burgdorferi-exposure
#15
Geetha Parthasarathy, Mario T Philipp
Lyme neuroborreliosis, caused by the gram-negative bacterium Borrelia burgdorferi, may affect the central and/or peripheral nervous systems. In previous studies, we showed that human oligodendrocytes exposed to the bacteria undergo apoptosis in an inflammatory environment, and that inflammatory pathways trigger cell-death pathways. We further demonstrated that several receptor tyrosine kinases were involved in triggering downstream effects, leading to inflammation and apoptosis. Toll-like receptors TLR2 and TLR5, which are commonly studied receptors in Lyme disease, only had a minimal role in inflammatory processes...
February 3, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29408443/for-whom-the-interferons-toll-tlr7-mediated-boosting-of-innate-and-adaptive-immunity-against-chronic-hbv-infection
#16
EDITORIAL
Bertram Bengsch, Robert Thimme
No abstract text is available yet for this article.
February 2, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29407574/pathogenicity-of-duck-hepatitis-a-virus-type-3-and-innate-immune-responses-of-the-ducklings-to-virulent-dhav-3
#17
Xuelian Zhang, Chong Cao, Zhehui Qu, Wenjing Zhang, Yue Liu, Haihui Qi, Chunxue Hao, Wenlong Zhang, Mingchun Gao, Junwei Wang, Bo Ma
Duck virus hepatitis caused by duck hepatitis A virus (DHAV) is an acute and contagious disease. To better understand the pathogenic mechanism of DHAV-3 in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DHAV-3 could infect many tissues, leading to pathological lesions, especially on the livers and spleen, and the host immune responses are activated in infection. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the livers and spleen, and antiviral innate immune response was established, but not sufficient to restrict the virus replication of lethal dose...
January 26, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29407424/expression-patterns-of-toll-like-receptors-in-the-ovine-corpus-luteum-during-the-early-pregnancy-and-prostaglandin-f2%C3%AE-induced-luteolysis
#18
Mehmet O Atli, Mehmet Kose, Mustafa Hitit, M Salih Kaya, Faruk Bozkaya
The aim of this study was to elucidate the expression profiles of Toll-like receptors (TLRs) in the ovine corpus luteum (CL) during early pregnancy and prostaglandin F2α (PGF2α)-induced luteolysis. For this purpose, multiparous Anatolian Merino ewes were selected and randomly allotted into cyclic (including those in the induced luteolysis group, n = 20) and pregnant (n = 12) groups. All of the ewes were scheduled to be slaughtered for predetermined days/hour during the estrous cycle, early pregnancy, and PGF2α induced luteolysis...
January 11, 2018: Theriogenology
https://www.readbyqxmd.com/read/29397456/immune-responses-of-mature-chicken-bone-marrow-derived-dendritic-cells-infected-with-newcastle-disease-virus-strains-with-differing-pathogenicity
#19
Bin Xiang, Wenxian Zhu, Yaling Li, Pei Gao, Jianpeng Liang, Di Liu, Chan Ding, Ming Liao, Yinfeng Kang, Tao Ren
Infection of chickens with virulent Newcastle disease virus (NDV) is associated with severe pathology and increased morbidity and mortality. The innate immune response contributes to the pathogenicity of NDV. As professional antigen-presenting cells, dendritic cells (DCs) play a unique role in innate immunity. However, the contribution of DCs to NDV infection has not been investigated in chickens. In this study, we selected two representative NDV strains, i.e., the velogenic NDV strain Chicken/Guangdong/GM/2014 (GM) and the lentogenic NDV strain La Sota, to investigate whether NDVs could infect LPS-activated chicken bone-derived marrow DCs (mature chicken BM-DCs)...
February 3, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29397183/short-communication-probiotic-induction-of-interleukin-10-and-interleukin-12-production-by-macrophages-is-modulated-by-co-stimulation-with-microbial-components
#20
Rumi Kaji, Junko Kiyoshima-Shibata, Satoshi Tsujibe, Masanobu Nanno, Kan Shida
Probiotic lactobacilli stimulate macrophages and dendritic cells to secrete cytokines and thereby regulate the immune responses of the host. The balance of the IL-10 and IL-12 production induced by a probiotic is crucial for determining the direction of the immune response. In the present study, we examined the ability of microbial components to modify IL-10 and IL-12 production induced by a popular probiotic strain, Lactobacillus casei strain Shirota (LcS), which itself predominantly induces IL-12 production...
January 31, 2018: Journal of Dairy Science
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