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Stephanie K Tankou, Keren Regev, Brian C Healy, Emily Tjon, Luca Laghi, Laura M Cox, Pia Kivisäkk, Isabelle V Pierre, Hrishikesh Lokhande, Roopali Gandhi, Sandra Cook, Bonnie Glanz, James Stankiewicz, Howard L Weiner
OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy...
April 20, 2018: Annals of Neurology
Rashi Singhal, Sheetal Chawla, Harish Batra, Sameer Gupta, Amrita Ojha, Deepak K Rathore, Tulika Seth, Prasenjit Guchhait
The distinct response shown by different phenotypes of macrophages and monocytes under various clinical conditions have put the heterogeneity of these cells into focus of investigation for several diseases. Recently we have described that after engulfing Hb-activated platelets, classical monocytes differentiated into pro-inflammatory phenotypes, which were abundant in the circulation of PNH and SCD patients. Our current study shows that upon engulfment of Hb-activated platelets, monocytes differentiate into M1-macrophages under M1-polarization stimulus (GM-CSF, IFN-γ+LPS)...
April 20, 2018: European Journal of Immunology
Juan José Muñoz, Javier García-Ceca, Sara Montero-Herradón, Beatriz Sánchez Del Collado, David Alfaro, Agustín Zapata
For a long time, the effects of distinct Eph tyrosine kinase receptors and their ligands, ephrins on the structure, immunophenotype, and development of thymus and their main cell components, thymocytes (T) and thymic epithelial cells (TECs), have been studied. In recent years, the thymic phenotype of mutant mice deficient in several Ephs and ephrins B has been determined. Remarkably, thymic stroma in these animals exhibits important defects that appear early in ontogeny but little alterations in the proportions of distinct lymphoid cell populations...
2018: Frontiers in Endocrinology
Joanne K Gardner, Scott M J Cornwall, Arthur W Musk, John Alvarez, Cyril D S Mamotte, Connie Jackaman, Anna K Nowak, Delia J Nelson
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation...
2018: PloS One
Gayeon Won, Seong Kug Eo, Sang-Youel Park, Jin Hur, John Hwa Lee
We previously genetically engineered a Salmonella Typhi bacterial ghost (STG) as a novel inactivated vaccine candidate against typhoid fever. The underlying mechanism employed by the ghost to stimulate the adaptive immune response remains to be investigated. In this study, we aimed to evaluate the immunostimulatory effect of STG on mouse bone marrow-derived dendritic cells (BMDCs) and its activation of the adaptive immune response in vitro . Immature BMDCs were stimulated with STG, which efficiently stimulated maturation events in BMDCs, as indicated by up-regulated expression of CD40, CD80, and MHC-II molecules on CD11+ BMDCs...
April 12, 2018: Journal of Veterinary Science
Shaowei Zhan, Jing Zheng, Haixia Zhang, Mingdong Zhao, Xianbing Liu, Yuzhu Jiang, Chunyan Yang, Liqin Ren, Zhiqiang Liu, Xuemei Hu
Toxoplasma gondii ( T. gondii ) infection in early pregnancy can result in miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central inhibitory receptor in uterine dendritic cells (uDCs) that plays essential immune-regulatory roles at the maternal-fetal interface. In this study, T. gondii -infected human primary uDCs and T. gondii -infected LILRB4-/- pregnant mice were utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were explored in the development of abnormal pregnancy outcomes following T...
2018: Frontiers in Microbiology
Kevin A Bockerstett, Chun Fung Wong, Sherri Koehm, Eric L Ford, Richard J DiPaolo
The ability to analyze individual epithelial cells in the gastric mucosa would provide important insight into gastric disease, including chronic gastritis and progression to gastric cancer. However, the successful isolation of viable gastric epithelial cells (parietal cells, neck cells, chief cells, and foveolar cells) from gastric glands has been limited due to difficulties in tissue processing. Furthermore, analysis and interpretation of gastric epithelial cell flow cytometry data has been difficult due to the varying sizes and light scatter properties of the different epithelial cells, high levels of autofluorescence, and poor cell viability...
April 6, 2018: International Journal of Molecular Sciences
Ken Takashima, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Stimulator of interferon genes (STING) is an essential molecule for the production of type I interferon (IFN), and other inflammatory cytokines, in response to cytosolic DNA. STING contributes to host defense against infection and anti-tumor responses. Previous reports have demonstrated that STING signaling is required by the adaptor Toll-IL-1 receptor-containing adaptor molecule-1 (TICAM-1), which has been identified as a TLR3-adaptor molecule using mouse embryonic fibroblasts. Here, we demonstrate that TICAM-1 does not affect STING-mediated innate immune responses, as increases in the mRNA expression levels of IFN-β, IL-6, and CCL5 were observed in bone marrow-derived or splenic myeloid cells...
April 5, 2018: Biochemical and Biophysical Research Communications
Juan Yun, Tong Xiao, Lei Zhou, Roger W Beuerman, Juanjuan Li, Yuan Zhao, Amir Hadayer, Xiaomin Zhang, Deming Sun, Henry J Kaplan, Hui Shao
Purpose: To investigate the role of damage-associated molecular patterns (DAMPs) in recurrent experimental autoimmune uveitis (EAU). Methods: Recurrent EAU was induced in Lewis rats by interphotoreceptor retinoid-binding protein (IRBP) R16-peptide specific T cells (tEAU). Aqueous humor and serum samples were kinetically collected and DAMPs examined by quantitative proteomics, Western blot analysis, and ELISA. tEAU rats were treated with S100 inhibitor paquinimod followed by disease evaluation...
March 1, 2018: Investigative Ophthalmology & Visual Science
K H Simons, Z Aref, H A B Peters, S P Welten, A Y Nossent, J W Jukema, J F Hamming, R Arens, M R de Vries, P H A Quax
BACKGROUND: T cells have a distinctive role in neovascularization, which consists of arteriogenesis and angiogenesis under pathological conditions and vasculogenesis under physiological conditions. However, the role of co-stimulation in T cell activation in neovascularization has yet to be established. The aim of this study was to investigate the role T cell co-stimulation and inhibition in angiogenesis, arteriogenesis and vasculogenesis. METHODS AND RESULTS: Hind limb ischemia was induced by double ligation of the left femoral artery in mice and blood flow recovery was measured with Laser Doppler Perfusion Imaging in control, CD70-/- , CD80/86-/- , CD70/80/86-/- and CTLA4+/- mice...
June 1, 2018: International Journal of Cardiology
Randi B Gombos, Ana Gonzalez, Mariana Manrique, Dhan Chand, David Savitsky, Benjamin Morin, Ekaterina Breous-Nystrom, Christopher Dupont, Rebecca A Ward, Cornelia Mundt, Benjamin Duckless, Hao Tang, Mark A Findeis, Andrea Schuster, Jeremy D Waight, Dennis Underwood, Christopher Clarke, Gerd Ritter, Taha Merghoub, David Schaer, Jedd D Wolchok, Marc van Dijk, Jennifer S Buell, Jean-Marie Cuillerot, Robert Stein, Elise E Drouin, Nicholas S Wilson
CTLA-4 and CD28 exemplify a co-inhibitory and co-stimulatory signaling axis that dynamically sculpts the interaction of antigen-specific T cells with antigen-presenting cells. Anti-CTLA-4 antibodies enhance tumor-specific immunity through a variety of mechanisms including: blockade of CD80 or CD86 binding to CTLA-4, repressing regulatory T cell function and selective elimination of intratumoral regulatory T cells via an Fcγ receptor-dependent mechanism. AGEN1884 is a novel IgG1 antibody targeting CTLA-4. It potently enhanced antigen-specific T cell responsiveness that could be potentiated in combination with other immunomodulatory antibodies...
2018: PloS One
Anquan Liu, Johan Frostegård
BACKGROUND: Activated T cells and dendritic cells (DCs) occur in atherosclerotic plaques. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR), and results in increased LDL-levels. We here investigate immune effects of PCSK9 on OxLDL induced DC maturation and T cell activation. METHODS: T cells were isolated from carotid specimens of patients undergoing carotid endarterectomy, or from peripheral blood of healthy individuals. Human peripheral blood monocytes were differentiated into DCs...
April 4, 2018: Journal of Internal Medicine
Nathalie J Vielle, Beatrice Zumkehr, Obdulio García-Nicolás, Fabian Blank, Miloš Stojanov, Didier Musso, David Baud, Artur Summerfield, Marco P Alves
While Zika virus (ZIKV) circulated for decades (African lineage strains) without report of outbreaks and severe complications, its emergence in French Polynesia and subsequently in the Americas (Asian lineage strains) was associated with description of severe neurological defects in newborns/neonates and adults. With the aim to identify virus lineage-dependent factors, we compared cell susceptibility, virus replication, cell death and innate immune responses following infection with two African and three contemporary Asian lineage strains of ZIKV...
April 3, 2018: Scientific Reports
Bruna F Pinto, Nayara I Medeiros, Andrea Teixeira-Carvalho, Silvana M Eloi-Santos, Tereza C M Fontes-Cal, Débora A Rocha, Walderez O Dutra, Rodrigo Correa-Oliveira, Juliana A S Gomes
In the chronic phase of Chagas disease, 60% of the patients develop the asymptomatic form known as indeterminate (IND). The remaining 30% of the patients develop a life-threatening form in which digestive and/or cardiac (CARD) alterations take place. The mechanisms underlying the development of severe forms of Chagas disease remain poorly understood. It is well known that interactions between immune cells such as monocytes and lymphocytes drive immune responses. Further, the co-stimulatory molecules CD80 and CD86 expressed by monocytes and subsets induce lymphocyte activation, thereby triggering cellular immune response...
2018: Frontiers in Immunology
Zhiqiang Yang, Yujian Liu, Xiaolei Zhou
RNA interference (RNAi) plays a potential role in organ transplantation. Small hairpin RNA (shRNA) is an artificial RNA molecule with a tight hairpin turn that can be used to silence the expression of a target gene. We constructed shRNA targeting on the cluster of differentiation 80 (CD80, B7-1) and the cluster of differentiation 86 (CD86, B7-2) and transfected it into dendritic cells (DCs). Fluorescence real-time PCR and flow cytometry confirmed the gene-silencing effect. Interleukin-2 (IL-2) mRNA expression level decreased in T cells that were cocultured with pB7-shRNA-transfected DCs...
March 26, 2018: Transplant Immunology
Larissa C Da Rosa, Joanne Boldison, Evy De Leenheer, Joanne Davies, Li Wen, F Susan Wong
AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets...
March 28, 2018: Diabetologia
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
Yohei Takeda, Masahiro Azuma, Kenji Funami, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Mycoplasma fermentans -derived diacylated lipoprotein M161Ag (MALP404) is recognized by human/mouse toll-like receptor (TLR) 2/TLR6. Short proteolytic products including macrophage-activating lipopeptide 2 (MALP2) have been utilized as antitumor immune-enhancing adjuvants. We have chemically synthesized a short form of MALP2 named MALP2s ( S -[2,3-bis(palmitoyloxy)propyl]-CGNNDE). MALP2 and MALP2s provoke natural killer (NK) cell activation in vitro but only poorly induce tumor regression using in vivo mouse models loading NK-sensitive tumors...
2018: Frontiers in Immunology
Serena Tedesco, Morena Zusso, Laura Facci, Annalisa Trenti, Carlotta Boscaro, Federica Belluti, Gian Paolo Fadini, Stephen D Skaper, Pietro Giusti, Chiara Bolego, Andrea Cignarella
Several studies suggest that curcumin and related compounds possess antioxidant and anti-inflammatory properties including modulation of lipopolysaccharide- (LPS-) mediated signalling in macrophage cell models. We here investigated the effects of curcumin and the two structurally unrelated analogues GG6 and GG9 in primary human blood-derived macrophages as well as the signalling pathways involved. Macrophages differentiated from peripheral blood monocytes for 7 days were activated with LPS or selective Toll-like receptor agonists for 24 h...
2018: Mediators of Inflammation
Chen Ling, Xiaorong Liu, Ying Shen, Zhi Chen, Jianfeng Fan, Yeping Jiang, Qun Meng
BACKGROUND: The level of urinary cluster of differentiation 80 (uCD80) is elevated in most children with minimal change disease (MCD) as opposed to focal segmental glomerulosclerosis (FSGS) during the acute phase. The objective of this follow-up study was to evaluate whether uCD80 elevation is actually associated with MCD and whether it signals better prognosis. METHODS: We evaluated uCD80 levels and a series of putative progression factors in a cohort of 64 patients with nephrotic syndrome (NS) seen between 2011 and 2016...
March 22, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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