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Stanislava Stanojević, Ivana Ćuruvija, Veljko Blagojević, Raisa Petrović, Vesna Vujić, Mirjana Dimitrijević
Rats of Albino Oxford (AO) strain in our animal facility exhibit a longer average healthy life span than rats of Dark Agouit (DA) strain. Since chronic activation of macrophages contributes to chronic low level inflammation common in older age, elucidation of the changes in middle-aged rats could be useful in prevention of unbalanced inflammatory response in advanced age. We have analysed the phenotype of unelicited and thioglycollate-elicited peritoneal macrophages from young and middle-aged DA and AO rats and tested functions of these cells following stimulation with lipopolysaccharide (LPS) in vitro...
October 15, 2016: Experimental Gerontology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Kaitlyn Sadtler, Brian W Allen, Kenneth Estrellas, Franck Housseau, Drew M Pardoll, Jennifer H Elisseeff
The immune system mediates tissue growth and homeostasis and is the first responder to injury or biomaterial implantation. Recently, it has been appreciated that immune cells play a critical role in wound healing and tissue repair and should thus be considered as potentially beneficial particularly in the context of scaffolds for regenerative medicine. Here, we present a flow cytometric analysis of cellular recruitment to tissue-derived extracellular matrix scaffolds where we quantitatively describe the infiltration and polarization of several immune subtypes including macrophages, dendritic cells, neutrophils, monocytes, T cells, and B cells...
October 13, 2016: Tissue Engineering. Part A
Wilbur H Chen, Marcela F Pasetti, Rajan P Adhikari, Holly Baughman, Robin Douglas, Jill El-Khorazaty, Nancy Greenberg, Frederick W Holtsberg, Grant C Liao, Mardi K Reymann, Xiaolin Wang, Kelly L Warfield, M Javad Aman
: Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB), containing 3 distinct mutations in the MHCII binding site, was combined with Alhydrogel as a potential parenteral vaccine named STEBVax.Consenting healthy adult volunteers, age 23-38 years, participated in a first-in-human open label dose-escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg...
October 5, 2016: Clinical and Vaccine Immunology: CVI
Sandra A Acosta, Naoki Tajiri, Paul R Sanberg, Yuji Kaneko, Cesar V Borlongan
In testing the hypothesis of Alzheimer's disease (AD)-like pathology in late stage traumatic brain injury (TBI), we evaluated AD pathological markers in late stage TBI model. Sprague-Dawley male rats were subjected to moderate controlled cortical impact (CCI) injury, and 6 months later euthanized and brain tissues harvested. Results from H&E staining revealed significant 33% and 10% reduction in the ipsilateral and contralateral hippocampal CA3 interneurons, increased MHCII-activated inflammatory cells in many gray matter (8-20-fold increase) and white matter (6-30-fold increased) regions of both the ipsilateral and contralateral hemispheres, decreased cell cycle regulating protein marker by 1...
October 4, 2016: Journal of Cellular Physiology
Timothy M Williams, Andrea F Wise, Daniel S Layton, Sharon D Ricardo
BACKGROUND AND AIM: Kidney ischemia/reperfusion (IR) injury is characterised by tubular epithelial cell (TEC) death and an inflammatory response involving cytokine production and immune cell infiltration. In various kidney diseases, increased macrophage numbers correlate with injury severity and poor prognosis. However, macrophage plasticity enables a diverse range of functions, including wound healing, making them a key target for novel therapies. This study aimed to comprehensively characterise the changes in myeloid and epithelial cells and the production of cytokines throughout the experimental IR model of acute kidney injury to aid in the identification of targets to promote and enhance kidney regeneration and repair...
October 1, 2016: Nephrology
Emre Balta, Julian Stopp, Laura Castelletti, Henning Kirchgessner, Yvonne Samstag, Guido H Wabnitz
Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis and/or NETosis. Apart from these conventional roles, PMN also have immune-regulatory functions. They can transdifferentiate and upregulate MHCII as well as ligands for costimulatory receptors which enables them to behave as antigen presenting cells (APC). The initial step for activating T-cells is the formation of an immune synapse between T-cells and antigen-presenting cells). However, the immune synapse that develops at the PMN/T-cell contact zone is as yet hardly investigated due to the non-availability of methods for analysis of large number of PMN interactions...
September 27, 2016: Methods: a Companion to Methods in Enzymology
Ning Zhu, Xiaochen Lv, Yangyun Wang, Jingling Li, Yongming Liu, Wenfei Lu, Liecheng Yang, Jian Zhao, Fujun Wang, Leshuai W Zhang
Polysaccharides from different types of natural herbs have not been compared with each other to determine their differential potencies on innate immune response, such as maturation of dendritic cells (DC). In addition, the role of endocytosis of polysaccharides in DC maturation has not been explored previously. Polysaccharides isolated from Astragalus membranaceus (APS), Ganoderma lucidum (GLP) and Radix ophiopogonis (OGP) were characterized and applied in bone marrow derived DC. Compared to immature DC, three polysaccharides with immunoactivities showed elongated dendrites, decreased phagocytic abilities, phenotypic changes (CD40/MHCII/CD80/CD86) and increased level of nitric oxide (NO) in a dose dependent manner...
October 7, 2016: International Journal of Biological Macromolecules
Adrienne M Antonson, Emily C Radlowski, Marcus A Lawson, Jennifer L Rytych, Rodney W Johnson
Maternal infection during pregnancy increases risk for neurodevelopmental disorders and reduced stress resilience in offspring, but the mechanisms are not fully understood. We hypothesized that piglets born from gilts infected with a respiratory virus during late gestation would exhibit aberrant microglia activity, cognitive deficits and reduced sociability. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV; 5 x 10(5) TCID50 of live PRRSV) or saline at gestational day 76...
September 17, 2016: Brain, Behavior, and Immunity
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Yfke Pasman, Daniele Merico, Azad K Kaushik
With an objective to understand natural development of bovine neonatal immunity, we analyzed 18 RNA-seq libraries from peripheral blood lymphocytes of three neonatal calves pre- (day 0) and post-colostrum (7, 14 and 28) uptake as compared to their dams. A significant global shift in neonatal transcriptome occurs within first week post-birth, in contrast to dams, with an upregulation of 717 genes. Global pathway analysis of the transcriptome revealed 110 differentially expressed immune-related genes, such as, complement, MHCII, chemokine receptors, defensins and cytokines, at birth...
September 3, 2016: Developmental and Comparative Immunology
Scott D Zawieja, Wei Wang, Sanjukta Chakraborty, David C Zawieja, Mariappan Muthuchamy
The intrinsic lymphatic pump is critical to proper lymph transport and is impaired in models of the metabolic syndrome (MetSyn). Lymphatic contractile inhibition under inflammatory conditions has been linked with elevated nitric oxide (NO) production by activated myeloid-derived cells. We utilized a high fructose-fed rat model of MetSyn to test our hypothesis that inhibition of the MLV pump function in MetSyn animals was dependent on NO and was associated with altered macrophage recruitment and polarization within the mesenteric lymphatic vessels (MLV)...
September 2, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Juan Pablo Mackern-Oberti, Evelyn L Jara, Claudia A Riedel, Alexis M Kalergis
Hormonal homeostasis is crucial for keeping a competent and healthy immune function. Several hormones can modulate the function of various immune cells such as dendritic cells (DCs) by influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens. Hormones, such as estrogens, prolactin, progesterone and glucocorticoids may profoundly affect DCs differentiation, maturation and function leading to either a pro-inflammatory or an anti-inflammatory (or tolerogenic) phenotype...
September 1, 2016: Archivum Immunologiae et Therapiae Experimentalis
Doaa A Ghareeb, Eiman H Elwakeel, Rowaida Khalil, Mina S Aziz, Maha A El Demellawy
BACKGROUND: Virus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and consequently chronic infection establishment. The present study reports an advanced hepatitis C virus (HCV) therapeutic vaccine model based on In vivo enrichment of DCs with barberry ethanolic crude extract (BCE) then pulsing them with HCV core protein. METHODS: DCs were enriched by BCE intravenous injection in BALB/c mice. Vaccine efficiency was assessed by flow cytometric analysis of splenocytes of immunized mice, cytokine profiling, cytotoxic T lymphocyte assay, and humoral immune response assessment...
2016: BMC Complementary and Alternative Medicine
Bianca Mendes Souza, Tatiane Melo Preisser, Vanessa Bastos Pereira, Meritxell Zurita-Turk, Camila Prósperi de Castro, Vanessa Pecini da Cunha, Rafael Pires de Oliveira, Ana Cristina Gomes-Santos, Ana Maria Caetano de Faria, Denise Carmona Cara Machado, Jean-Marc Chatel, Vasco Ariston de Carvalho Azevedo, Philippe Langella, Anderson Miyoshi
BACKGROUND: Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease...
2016: Microbial Cell Factories
Yosuke Kumamoto, Joao Paulo G Camporez, Michael J Jurczak, Marya Shanabrough, Tamas Horvath, Gerald I Shulman, Akiko Iwasaki
Mononuclear phagocytes (MNPs) are a highly heterogeneous group of cells that play important roles in maintaining the body's homeostasis. Here, we found CD301b (also known as MGL2), a lectin commonly used as a marker for alternatively activated macrophages, was selectively expressed by a subset of CD11b(+)CD11c(+)MHCII(+) MNPs in multiple organs including adipose tissues. Depleting CD301b(+) MNPs in vivo led to a significant weight loss with increased insulin sensitivity and a marked reduction in serum Resistin-like molecule (RELM) α, a multifunctional cytokine produced by MNPs...
September 20, 2016: Immunity
Alan J Sokoloff, Megan Douglas, Jill A Rahnert, Thomas Burkholder, Kirk A Easley, Qingwei Luo
INTRODUCTION: Equivocal decline of tongue muscle performance with age is compatible with resistance of the tongue to sarcopenia, the loss of muscle volume and function that typically occurs with aging. To test this possibility we characterized anatomical and molecular indices of sarcopenia in the macaque tongue muscle styloglossus (SG). METHODS: We quantified myosin heavy chain (MHC), muscle fiber MHC phenotype and size and total and phosphorylated growth- and atrophy-related proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblot and immunohistochemistry (IHC) in the SG in twenty-four macaque monkeys (Macaca rhesus, age range 9months to 31years) categorized into Young (<8years of age), Middle-aged (15-21years of age) and Old (>22years of age) groups...
November 2016: Experimental Gerontology
Séverine Ciré, Sylvie Da Rocha, Maxime Ferrand, Mary K Collins, Anne Galy
Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II(+) cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4...
October 4, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Kyle D Wilson, Sonja J Stutz, Lorenzo F Ochoa, Gustavo A Valbuena, Petra D Cravens, Kelly T Dineley, Gracie Vargas, Robin Stephens
BACKGROUND: Cerebral malaria is one of the most severe complications of Plasmodium falciparum infection and occurs mostly in young African children. This syndrome results from a combination of high levels of parasitaemia and inflammation. Although parasite sequestration in the brain is a feature of the human syndrome, sequestering strains do not uniformly cause severe malaria, suggesting interplay with other factors. Host genetic factors such as mutations in the promoters of the cytokines IL-10 and TNF are also clearly linked to severe disease...
2016: Malaria Journal
Annette R Rodriguez, Jieh-Juen Yu, Christopher Navara, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Understanding innate immune intercellular communication following microbial infection remains a key biological issue. Using live cell imaging, we demonstrate that mast cells actively extend cellular projections to sample the macrophage periphery during Francisella tularensis LVS infection. Mast cell MHCII(hi) expression was elevated from less than 1% to 13% during LVS infection. Direct contact during co-culture with macrophages further increased mast cell MHCII(hi) expression to approximately 87%. Confocal analyses of the cellular perimeter revealed mast cell caspase-1 was localized in close proximity with FcɛRI in uninfected mast cells, and repositioned to clustered regions upon LVS infection...
October 2016: Innate Immunity
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