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Innate Immunity

Hamid Shegarfi, Kevin P Kane, Janne Nestvold
Murine NK cell Ly49 receptors, functionally analogous to KIRs in humans recognize MHC class I molecules and play a key role in controlling NK cell function. We have previously shown that the paired activating Ly49s4 and inhibitory Ly49i4 receptors recognize undefined non-classical MHC-Ib ligands from the RT1-CE region in rats. Here, the RT1-CE16 gene of the RT1d haplotype was stably transfected into the mouse RAW macrophage cell line, termed RAW-CE16d cells. Combining RAW-CE16d cells with Ly49 expressing reporter cells demonstrated Ly49i4 and Ly49s4 specificity for CE16d ...
May 2018: Innate Immunity
Daniel Busch, Amar Kapoor, Pia Rademann, Frank Hildebrand, Soheyl Bahrami, Christoph Thiemermann, Marcin F Osuchowski
Activation of peroxisome proliferator-activated receptor (PPAR)-β/δ reduces tissue injury in murine endotoxemia. We hypothesized that the PPAR-β/δ-agonist GW0742 improves long-term outcome after sepsis caused by cecal ligation and puncture (CLP). Fifty-one CD-1 female mice underwent CLP and received either vehicle (control), GW0742 (0.03 mg/kg/injection; five post-CLP i.v. injections), GSK0660 (PPAR-β/δ-antagonist) or both and were monitored for 28 d. Another 20 CLP mice treated with GW0742 and vehicle were sacrificed 24 h post-CLP to assess coagulopathy...
May 2018: Innate Immunity
Qirui Li, Lingyun Li, Xiaoyuan Fei, Yuanyue Zhang, Chang Qi, Shuyao Hua, Feili Gong, Min Fang
Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice. Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin...
May 2018: Innate Immunity
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...
May 2018: Innate Immunity
Cortney L Armstrong, Christopher K Klaes, Aruna Vashishta, Richard J Lamont, Silvia M Uriarte
Neutrophils operate at the site of injury or inflammation in the periodontal pocket to ensure periodontal health and clearance of bacterial pathogens. Filifactor alocis is recently identified as a potential periodontal pathogen, and in this study, we assessed the formation of neutrophil extracellular traps (NETs), in response to the presence of the organism . NET formation by human neutrophils was not induced when challenged with F. alocis, independent of opsonization, viability, time, or bacterial dose. F...
May 2018: Innate Immunity
Shuting Cao, Qianhui Zhang, ChunChun Wang, Huan Wu, Lefei Jiao, Qihua Hong, Caihong Hu
Here we investigated the influence of LPS-induced gut injury on antioxidant homeostasis, mitochondrial (mt) function and the level of mitophagy in piglets. The results showed that LPS-induced intestinal injury decreased the transepithelial electrical resistance, increased the paracellular permeability of F1TC dextran 4 kDa, and decreased the expression of claudin-1, occludin and zonula occludens-1 in the jejunum compared with the control group. LPS decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde in the jejunum...
May 2018: Innate Immunity
Jingzhu Lv, Xiaojie Zhang, Caizhi Wang, Hongtao Wang, Ting Wang, Zhongqing Qian
Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients with PE exhibit systemic high oxidative stress status and inflammatory immune activation. This study aims to define the role of H2 O2 in the activation of neutrophils and T lymphocytes in PE patients. CD3+ /HLA-DR+ cells in blood from PE patients are remarkably increased compared with those of normal non-pregnancies or normal pregnancies, while the percentage of CD3+ /CD62L+ cells is significantly reduced in PE patients compared to normal pregnancies...
May 2018: Innate Immunity
Muki Shehu Shey, Avuyonke Balfour, Katalin Andrea Wilkinson, Graeme Meintjes
APCs such as monocytes and dendritic cells are among the first cells to recognize invading pathogens and initiate an immune response. The innate response can either eliminate the pathogen directly, or through presentation of Ags to T cells, which can help to clear the infection. Mucosal-associated invariant T (MAIT) cells are among the unconventional T cells whose activation does not involve the classical co-stimulation during Ag presentation. MAIT cells can be activated either via presentation of unconventional Ags (such as riboflavin metabolites) through the evolutionarily conserved major histocompatibility class I-like molecule, MR1, or directly by cytokines such as IL-12 and IL-18...
May 2018: Innate Immunity
Reham Hammad Mahmoud Hammad, Dina Hossam El Dine Hamed, Mona Abd El Rahman Eldosoky, Ashraf Abd Elmonem Sayed Ahmad, Hanan Mohsen Osman, Heba Mohamed Abd Elgalil, Mahmoud Mohsen Mahmoud Hassan
Childhood asthma represents a worldwide problem, involving genetic, immune defense and environmental components. MicroRNAs (miRs) are non-coding, single-stranded RNAs involved in immune regulation. The aim was to evaluate clinical potential of plasma miR-21 and miR-146a involved in T helper differentiation in childhood asthma and non-asthmatic controls. Group 1 consisted of 27 asthmatic children receiving inhaled corticosteroids (ICSs), which was compared to group 2 with 21 healthy control children. All patients were assessed by pulmonary function tests...
April 2018: Innate Immunity
Antoni W Różalski
Professor Krystyna Kotełko was working as a microbiologist at the University of Łódź (Poland). Her main object of study was the LPS (endotoxin) of opportunistic urinary pathogens from the genus Proteus. She demonstrated, for the first time, the presence of uronic acids and amino acids, as well as two heptoses (L- glycero-D- manno-heptose and D- glycero-D- manno-heptose) and hexosamines in Proteus LPS, and developed a classification scheme of the Proteus LPS into chemotypes. Prof Kotełko also initiated studies on the chemical structure of Proteus O-specific polysaccharide and investigations on the serological specificity of this part of LPS, as well its core region...
April 2018: Innate Immunity
Nailia R Khasbiullina, Nadezhda V Shilova, Maxim E Navakouski, Alexey Yu Nokel, Yuri A Knirel, Ola Blixt, Nicolai V Bovin
Innate immunity natural Abs (NAbs) execute a number of functions, including protection and surveillance. Despite active research, the stimuli that induce the formation of NAbs are still described only hypothetically. Here, we compared repertoires of anti-glycan Abs in the peripheral blood of mice that received per os various bacteria. The repertoires of Abs of mice primed in this way were compared using a microarray that included about 350 glycans, as well as 150 bacterial polysaccharides. Sterile mice did not possess anti-glycan Abs...
April 2018: Innate Immunity
Ewelina Gowin, Bogna Świątek-Kościelna, Ewelina Kałużna, Ewa Strauss, Jacek Wysocki, Jerzy Nowak, Michał Michalak, Danuta Januszkiewicz-Lewandowska
The aim of this study is to describe the prevalence of single single-nucleotide polymorphisms (SNPs) as well as their combinations in genes encoding proteins involved in the immune response in children with bacterial meningitis. The prospective study group consisted of 39 children with bacterial meningitis and 49 family members surveyed between 2012 and 2016. Eleven SNPs in seven genes involved in immune response were analysed. The mean number of minor frequency alleles (MAF) of studied SNPs was lowest in the control group and highest in patients with pneumococcal meningitis...
April 2018: Innate Immunity
Nikita H Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P Doelger, Christopher S Navara, Lisa Y Armitige, Janakiram Seshu, Anthony P Sinai, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection...
April 2018: Innate Immunity
Mia Olsson, Lisa Bremer, Cecilia Aulin, Helena Erlandsson Harris
Hyaluronan (HA) is a large polymer and an important component of the extracellular matrix. During homeostasis, high molecular mass HA is the predominant form, but upon inflammation, degradation products of HA accumulate. These HA fragments (HA-fs) have been reported to possess pro-inflammatory activities and thus act as alarmins, notifying immune cells of danger via TLR4 and CD44. HA is found in large quantities in synovial joint fluid. In order to reveal a potential role of HA-fs in arthritis pathogenesis, the in vitro effects of HA of various molecular masses (from 1680 kDa to oligosaccharide HA) on synovial fibroblasts and chondrocytes from rheumatoid arthritis patients, and on peripheral blood mononuclear cells from healthy donors, were investigated...
February 2018: Innate Immunity
XiaoWei Qian, Hang Zhao, XinZhong Chen, Jun Li
Elastase released by neutrophils is critical for eliminating Gram-negative bacteria. Ca2+ influx plays a key role in elastase release and bacterial clearance in neutrophils. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable cation channel highly expressed in neutrophils. Here, we explore the role and possible mechanism of TRPM2 in bacterial clearance in TRPM2 knockout (TRPM2-KO) mice neutrophils. After exposure to Escherichia coli, TRPM2-KO bone marrow neutrophils (BMNs) had increased bacterial burden and decreased elastase release...
February 2018: Innate Immunity
Sarah L Caddy, Meng Wang, Pramila Krishnamurthy, Benjamin Uttenthal, Anita Chandra, Charles Crawley, Leo C James
Viral infection is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplant (HSCT), with up to one in four deaths directly linked to viral disease. Whilst awaiting lymphocyte reconstitution post-HSCT, the innate antiviral immune response is the first line of defense against invading viruses. Several novel innate viral-sensing pathways have recently been characterized, but their physiological importance in humans is poorly understood. We analyzed a panel of innate viral-sensor genes in HSCT patients, and assessed whether differences in innate antiviral responses could account for variation in susceptibility to viral infections...
February 2018: Innate Immunity
Hans Christian D Aass, Marit Hellum, Anne-Marie Siebke Trøseid, Petter Brandtzaeg, Jens Petter Berg, Reidun Øvstebø, Carola Elisabeth Henriksson
Levels of bacterial LPS, pro-inflammatory cytokines and IL-10 are related to the severity of meningococcal septicaemia. Patients infected with a Neisseria meninigitidis lpxL1 mutant ( Nm-mutant) with penta-acylated lipid A present with a milder meningococcal disease than those infected with hexa-acylated Nm wild type ( Nm-wt). The aim was to compare the pro-inflammatory responses after ex vivo incubation with the heat-inactivated Nm-wt or the Nm-mutant in citrated whole blood, and the modulating effects of IL-10...
February 2018: Innate Immunity
Yoshitake Desaki, Kana Miyata, Maruya Suzuki, Naoto Shibuya, Hanae Kaku
Plants possess the ability to recognize microbe-associated molecular patterns (MAMPs) and PAMPs through the PRRs, and initiate pattern-triggered immunity. MAMPs are derived from cell-envelope components, secreted materials and cytosolic proteins from bacteria, oomycetes or fungi, and some MAMPs play a similar function in the innate immunity in mammals. Chitin is a representative fungal MAMP and triggers defense signaling in a wide range of plant species. The chitin receptors CEBiP and CERK1 on the plasma membrane have LysM (lysin motif) in their ectodomains...
February 2018: Innate Immunity
Junhui He, Mingchong Sun, Sujian Tian
Lupus nephritis (LN) is a multifactorial event that contributes to the long-term mortality of systemic lupus erythematosus (SLE). Activation of NLRP3 inflammasome has been known to play a role in SLE pathogenesis. We evaluated the renal protection effects of procyanidin B2 (PCB2) and the involvement of NLRP3 in a mouse model involving MRL/lpr and MRL/MpJ mice. Kidney injury was evaluated by measuring the renal clinical and pathological features, renal immune complex deposition, and serum anti-double-stranded (anti-dsDNA) Abs...
January 1, 2018: Innate Immunity
Yohei Takeda, Masahiro Azuma, Ryoko Hatsugai, Yukari Fujimoto, Masahito Hashimoto, Koichi Fukase, Misako Matsumoto, Tsukasa Seya
The TLR2 agonist, dipalmitoyl lipopeptide (Pam2LP), has been used as an immune adjuvant without much success. Pam2LP is recognised by TLR2/6 receptors in humans and in mice. This study examined the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT-I assay system, where a library of synthetic Pam2LP was utilised from the Staphylococcus aureus database. Ag-specific CTL expansion and IFN-γ levels largely depended on the Pam2LP peptide sequence. The first Aa is cysteine (Cys), which has an active SH residue to bridge fatty acids, and the second and third Aa are hydrophilic or non-polar...
January 1, 2018: Innate Immunity
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