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Sara Montserrat-Sangrà, Laura Ordeix, Pamela Martínez-Orellana, Laia Solano-Gallego
Canine leishmaniosis has a wide range of disease severity from mild (stage I), to severe (stages II-III), or very severe disease (stage IV). The objective of the study was to evaluate and compare serum antibody levels, Leishmania infantum specific IFN-γ production and TLR2 and TLR4 transcripts in non-stimulated blood from dogs with different clinical stages at the time of diagnosis as well as blood parasitemia. Enzyme-Linked ImmunoSorbent Assay (ELISAs) were performed to determine serum antibody levels and IFN-γ production and quantitative polymerase chain reaction ( q PCRs) in order to determine blood parasite load and TLR2 and TLR4 transcripts...
March 16, 2018: Veterinary Sciences
Neha M Sahasrabudhe, Martin Beukema, Lingmin Tian, Berit Troost, Jan Scholte, Erik Bruininx, Geert Bruggeman, Marco van den Berg, Anton Scheurink, Henk A Schols, Marijke M Faas, Paul de Vos
Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered...
2018: Frontiers in Immunology
Marliane Batista Campos, Luciana Vieira do Rêgo Lima, Ana Carolina Stocco de Lima, Thiago Vasconcelos Dos Santos, Patrícia Karla Santos Ramos, Claudia Maria de Castro Gomes, Fernando Tobias Silveira
Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L...
2018: PloS One
Peter Moritz Becher, Svenja Hinrichs, Nina Fluschnik, Jan K Hennigs, Karin Klingel, Stefan Blankenberg, Dirk Westermann, Diana Lindner
Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Although optimal medical care and treatment is widely available, the prognosis of patients with HF is still poor. Toll-like receptors (TLRs) are important compartments of the innate immunity. Current studies have identified TLRs as critical mediators in cardiovascular diseases. In the present study, we investigated the involvement of TLRs and interferon (IFN) regulatory factors (IRFs) in different experimental HF models including viral myocarditis, myocardial ischemia, diabetes mellitus, and cardiac hypertrophy...
2018: PloS One
Yin-Feng Dong, Ruo-Bing Guo, Juan Ji, Lu-Lu Cao, Ling Zhang, Zheng-Zhen Chen, Ji-Ye Huang, Jin Wu, Jun Lu, Xiu-Lan Sun
Fingolimod (FTY720) is used as an immunosuppressant for multiple sclerosis. Numerous studies indicated its neuroprotective effects in stroke. However, the mechanism remains to be elucidated. This study was intended to investigate the mechanisms of phosphorylated FTY720 (pFTY720), which was the principle active molecule in regulating astrocyte-mediated inflammatory responses induced by oxygen-glucose deprivation (OGD). Results demonstrated that pFTY720 could protect astrocytes against OGD-induced injury and inflammatory responses...
March 13, 2018: Journal of Cellular and Molecular Medicine
Simon R Lea, Sophie L Reynolds, Manminder Kaur, Karen D Simpson, Simon R Hall, Edith M Hessel, Dave Singh
Background: COPD is a progressive inflammatory airway disease characterized by increased numbers of alveolar macrophages in the lungs. Bacterial colonization of the lungs is a common feature in COPD and can promote inflammation through continual and repeated Toll-like receptor (TLR) stimulation. We have studied the response of COPD alveolar macrophages to repetitive stimulation with TLR2 and TLR4 ligands. We investigated the effect of sequential stimulation with different ligands to determine whether this results in tolerance or amplification of the immune response...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Shaoyi Cai, Gengzheng Zhu, Xiaohong Cen, Jingjie Bi, Jingru Zhang, Xiaoshan Tang, Kun Chen, Kui Cheng
Toll-like receptor 2 (TLR2) can recognize pathogen-associated molecular patterns to defense against invading organisms and has been represents an attractive therapeutic target. Until today, none TLR2 small molecule antagonist have been developed in clinical trial. Herein, we designed and synthesized 50 N-benzylideneaniline compounds with the help of CADD. And subsequent in vitro studies leading to the optimized compound SMU-A0B13 with most potent inhibitory activity to TLR2 (IC50 =18.21 ± 0.87 μM)...
March 10, 2018: Bioorganic & Medicinal Chemistry
N Lacey, A Russell-Hallinan, C C Zouboulis, F C Powell
Rosacea is a common facial skin disorder affecting middle-aged adults. Its aetiology is unknown and pathogenesis uncertain. Activation of the host innate immune response has been identified as important. The Demodex mite population in the skin of these patients is significantly higher than in subjects with normal skin suggesting they may be of etiological importance in this disorder. Little is known of the role of these mites in human skin and their potential to interact with the host immune system has not been elucidated...
March 12, 2018: British Journal of Dermatology
Theodora A M Claushuis, Annelou I P Van Der Veen, Janneke Horn, Marcus J Schultz, Riekelt H Houtkooper, Cornelis Van 't Veer, Tom Van Der Poll
Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression...
March 12, 2018: Platelets
Yu Wang, Miao-Miao Zhang, Wei-Wei Huang, Shou-Quan Wu, Ming-Gui Wang, Xiao-Yan Tang, Andrew J Sandford, Jian-Qing He
Background: The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis . There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Methods: Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method...
2018: Frontiers in Immunology
A R Khosravi, H Shokri, S Hassan Al-Heidary, F Ghafarifar
OBJECTIVE: The aims of this study were to determine the role of live and heat-killed Aspergillus fumigatus conidia in releasing interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) and to express Toll-like receptor (Tlr)2 and Tlr4 genes. MATERIALS AND METHODS: Murine lung epithelial cells were incubated with live and heat-killed A. fumigatus conidia at 37°C for 6, 24 and 48h. After treatments, ELISA was performed to measure the concentrations of IL-25, IL-33 and TSLP in the supernatants...
March 7, 2018: Journal de Mycologie Médicale
Shanmao Cao, Lijie Zhu, Hongtao Nie, Minghao Yin, Gang Liu, Xiwu Yan
Crassadoma gigantea is an important commercial marine bivalve species in Baja California and Mexico. In this study, we have applied RNA-Seq technology to profile the transcriptome of the C. gigantea for the first time. A total of 80,832,518 raw reads were produced from a Illumina HiSeq4000 platform, and 77,306,198 (95.64%) clean reads were generated after trimming the adaptor sequences. The transcriptome assembled into 158,855 transcripts with an N50 size of 1995 bp and an average size of 1008 bp. A number of DNA repair related genes, such as MSH3, EGF, TGF, IGF, FGF, encoding different groups of growth factors were found in the transcriptome data of C...
March 7, 2018: Gene
Violeta D Alvarez-Jiménez, Kahiry Leyva-Paredes, Mariano García-Martínez, Luis Vázquez-Flores, Víctor Gabriel García-Paredes, Marcia Campillo-Navarro, Israel Romo-Cruz, Víctor Hugo Rosales-García, Jessica Castañeda-Casimiro, Sirenia González-Pozos, José Manuel Hernández, Carlos Wong-Baeza, Blanca Estela García-Pérez, Vianney Ortiz-Navarrete, Sergio Estrada-Parra, Jeanet Serafín-López, Isabel Wong-Baeza, Rommel Chacón-Salinas, Iris Estrada-García
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication...
2018: Frontiers in Immunology
Katharina Bröker, Julia Figge, Albert F Magnusen, Rudolf A Manz, Jörg Köhl, Christian M Karsten
B-1 cells constitute a unique subpopulation of lymphocytes residing mainly in body cavities like the peritoneal cavity (PerC) but are also found in spleen and bone marrow (BM). As innate-like B cells, they mediate first line immune defense through low-affinity natural IgM (nIgM) antibodies. PerC B-1 cells can egress to the spleen and differentiate into nIgM antibody-secreting plasma cells that recognize conserved exogenous and endogenous cellular structures. Homing to and homeostasis within the PerC are regulated by the chemokine CXCL13 released by PerC macrophages and stroma cells...
2018: Frontiers in Immunology
Xinhua Zhan, Boryana Stamova, Frank R Sharp
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex...
2018: Frontiers in Aging Neuroscience
Kyung-Joo Seong, Hyeong-Jun Kim, Bangrong Cai, Min-Suk Kook, Ji-Yeon Jung, Won-Jae Kim
The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia...
March 2018: Korean Journal of Physiology & Pharmacology
Won Jai Jung, Sang Yeub Lee, Sue In Choi, Byung-Keun Kim, Eun Joo Lee, Kwang Ho In, Min-Goo Lee
Airway sensory nerves are known to express several receptors and channels that are activated by exogenous and endogenous mediators that cause coughing. Toll-like receptor (TLR) s are expressed in nociceptive neurons and play an important role in neuroinflammation. However, there have been very few studies of TLR expression in lung-derived sensory neurons or their relevance to respiratory symptoms such as cough. We used the bleomycin-induced pulmonary fibrosis model to investigate the change in TLR expression in pulmonary neurons and the association of TLRs with transient receptor potential (TRP) channels in pulmonary neurons...
2018: PloS One
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
Rachel E Polando, Blake C Jones, Cristina Ricardo, James Whitcomb, Wibke Ballhorn, Mary Ann McDowell
AIMS: Leishmania enter macrophages through receptor mediated phagocytosis and survive the harsh environment of a phagolysosome. Here, we investigated the interaction between MR, TLR2, and Leishmania, and the subsequent impact on phagosome maturation. METHODS AND RESULTS: Leishmania parasites are able to delay phagosome maturation, not reaching full maturation until five hours post engulfment. Here, maturation of Leishmania major and L. donovani containing phagosomes proceeded as expected in the WT macrophages becoming LAMP1 positive by 6 hours...
March 6, 2018: Parasite Immunology
Mala Mahendroo
Cervical hyaluronan (HA) synthesis is robustly induced in late pregnancy in numerous species including women and mice. Recent evidence highlights the diverse and dynamic functions of HA in cervical biology that stem from its expression in the cervical stroma, epithelia and immune cells, changes in HA molecular weight and cell specific expression of HA binding partners. Mice deficient in HA in the lower reproductive tract confirm a structural role of HA to increase spacing and disorganization of fibrillar collagen, though this function is not critical for pregnancy and parturition...
March 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
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