scholarly journals Galectin-3 Modulates Immune and Inflammatory Responses during Helminthic Infection: Impact of Galectin-3 Deficiency on the Functions of Dendritic Cells

2007 ◽  
Vol 75 (11) ◽  
pp. 5148-5157 ◽  
Author(s):  
Laetitia Breuilh ◽  
François Vanhoutte ◽  
Josette Fontaine ◽  
Caroline M. W. van Stijn ◽  
Isabelle Tillie-Leblond ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Adaptive Immune Response ◽  
Chronic Phase ◽  
Cell Types ◽  
Experimental Models ◽  
Helminthic Infection ◽  
Galectin 3

ABSTRACT Galectin-3 (Gal-3) is a multifunctional β-galactoside-binding lectin that senses self-derived and microbial glycoconjugates. Although Gal-3 is important in immune reactions and host defense in some experimental models, the function of Gal-3 during helminthic diseases (e.g., schistosomiasis) is still elusive. We show that, compared to wild-type Schistosoma mansoni-infected mice, infected Gal-3−/− mice have a reduced number of T and B lymphocytes in the spleen, develop reduced liver granulomas at 7 weeks (acute phase) and 14 weeks (chronic phase) postinfection, and mount a biased cellular and humoral Th1 response. In an attempt to understand this latter phenomenon, we studied the role of endogenous Gal-3 in dendritic cells (DCs), the most potent antigen-presenting cells, both in vitro and in vivo. Although Gal-3 deficiency in DCs does not impact their differentiation and maturation processes, it greatly influences the strength (but not the nature) of the adaptive immune response that they trigger, suggesting that Gal-3 deficiency in some other cell types may be important during murine schistosomiasis. As a whole, this study implies that Gal-3 is a modulator of the immune/inflammatory responses during helminthic infection and reveals for the first time that Gal-3 expression in DCs is pivotal to control the magnitude of T-lymphocyte priming.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinjini Chakraborty ◽  
Veronika Eva Winkelmann ◽  
Sonja Braumüller ◽  
Annette Palmer ◽  
Anke Schultze ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Lung Damage ◽  
C5a Receptor ◽  
Cytokine Levels ◽  
Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

Chagas Disease Chemotherapy: What Do We Know So Far?

2021 ◽  
Vol 27 ◽  
Author(s):  
Aline Araujo Zuma ◽  
Wanderley de Souza
Keyword(s):  
Host Cell ◽  
Chagas Disease ◽  
Chronic Phase ◽  
Cell Types ◽  
Neglected Tropical Disease ◽  
Cell Type ◽  
Cure Rate ◽  
New Compounds

: Chagas disease is a Neglected Tropical Disease (NTD), and although endemic in Latin America, affects around 6-7 million people infected worldwide. The treatment of Chagas disease is based on benznidazole and nifurtimox, which are the only available drugs. However, they are not effective during the chronic phase and cause several side effects. Furthermore, BZ promotes cure in 80% of the patients in the acute phase, but the cure rate drops to 20% in adults in the chronic phase of the disease. In this review, we present several studies published in the last six years, which describes the antiparasitic potential of distinct drugs, from the synthesis of new compounds aiming to target the parasite, as well as the repositioning and the combination of drugs. We highlight several compounds for having shown results that are equivalent or superior to BZ, which means that they should be further studied, either in vitro or in vivo. Furthermore, we stand out the differences in the effects of BZ on the same strain of T. cruzi, which might be related to methodological differences such as parasite and cell ratios, host cell type and the time of adding the drug. In addition, we discuss the wide variety of strains and also the cell types used as a host cell, which makes it difficult to compare the trypanocidal effect of the compounds.

scholarly journals Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra Winning ◽  
Joachim Fandrey
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Mature Dendritic Cell ◽  
Innate And Adaptive Immunity ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Oxygen Shortage

Dendritic cells (DCs) are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia) which is often not considered in experimental settings. This review highlights how deeply hypoxia modulates human as well as mouse immature and mature dendritic cell functions. It tries to linkin vitroresults to actualin vivostudies and outlines how hypoxia-mediated shaping of dendritic cells affects the activation of (innate) immunity.

Regulation of angiopoietin expression by bacterial lipopolysaccharide

2008 ◽  
Vol 294 (5) ◽  
pp. L955-L963 ◽  
Author(s):  
Mahroo Mofarrahi ◽  
Thamir Nouh ◽  
Salman Qureshi ◽  
Loic Guillot ◽  
Dominique Mayaki ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Vascular Leakage ◽  
Saline Control ◽  
E Coli ◽  
Protein Levels ◽  
Angiopoietin 2

Angiopoietins are ligands for Tie-2 receptors and play important roles in angiogenesis and inflammation. While angiopoietin-1 (Ang-1) inhibits inflammatory responses, angiopoietin-2 (Ang-2) promotes cytokine production and vascular leakage. In this study, we evaluated in vivo and in vitro effects of Escherichia coli lipopolysaccharides (LPS) on angiopoietin expression. Wild-type C57/BL6 mice were injected with saline (control) or E. coli LPS (20 mg/ml ip) and killed 6, 12, and 24 h later. The diaphragm, lung, and liver were excised and assayed for mRNA and protein expression of Ang-1, Ang-2, and Tie-2 protein and tyrosine phosphorylation. LPS injection elicited a severalfold rise in Ang-2 mRNA and protein levels in the three organs. By comparison, both Ang-1 and Tie-2 levels in the diaphragm, liver, and lung were significantly attenuated by LPS administration. In addition, Tie-2 tyrosine phosphorylation in the lung was significantly reduced in response to LPS injection. In vitro exposure to E. coli LPS elicited cell-specific changes in Ang-1 expression, with significant induction in Ang-1 expression being observed in cultured human epithelial cells, whereas significant attenuation of Ang-1 expression was observed in response to E. coli LPS exposure in primary human skeletal myoblasts. In both cell types, E. coli LPS elicited substantial induction of Ang-2 mRNA, a response that was mediated in part through NF-κB. We conclude that in vivo endotoxemia triggers functional inhibition of the Ang-1/Tie-2 receptor pathway by reducing Ang-1 and Tie-2 expression and inducing Ang-2 levels and that this response may contribute to enhanced vascular leakage in sepsis.

scholarly journals Infection of Dendritic Cells by the Maedi-Visna Lentivirus

2000 ◽  
Vol 74 (21) ◽  
pp. 10096-10103 ◽  
Author(s):  
Susanna Ryan ◽  
Laurence Tiley ◽  
Ian McConnell ◽  
Barbara Blacklaws
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cell Types ◽  
Infected Sheep ◽  
In Vivo Model ◽  
Visna Virus ◽  
Afferent Lymph ◽  
Infection Experiments

ABSTRACT The early stages of lentivirus infection of dendritic cells have been studied in an in vivo model. Maedi-visna virus (MVV) is a natural pathogen of sheep with a tropism for macrophages, but the infection of dendritic cells has not been proven, largely because of the difficulties of definitively distinguishing the two cell types. Afferent lymphatic dendritic cells from sheep have been phenotypically characterized and separated from macrophages. Dendritic cells purified from experimentally infected sheep have been demonstrated not only to carry infectious MVV but also to be hosts of the virus themselves. The results of the in vivo infection experiments are supported by infections of purified afferent lymph dendritic cells in vitro, in which late reverse transcriptase products are demonstrated by PCR. The significance of the infection of afferent lymph dendritic cells is discussed in relation to the initial spread of lentivirus infection and the requirement for CD4 T cells.

scholarly journals Interleukin-1β, but not interleukin-6, enhances renal and systemic endothelin production in vivo

2008 ◽  
Vol 295 (2) ◽  
pp. F446-F453 ◽  
Author(s):  
Erika I. Boesen ◽  
Jennifer M. Sasser ◽  
Mohamed A. Saleh ◽  
William A. Potter ◽  
Mandy Woods ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Excretion Rate ◽  
Collecting Duct ◽  
Cell Types ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Subcutaneous Infusion ◽  
Medullary Collecting Duct

The inflammatory cytokines IL-1β and IL-6 have been shown to stimulate production of endothelin-1 (ET-1) by several cell types in vitro, but their effects on renal ET-1 production in vivo are not known. To test whether IL-1β and IL-6 stimulate renal ET-1 production and release in vivo, urine was collected from male C57BL/6 mice over 24-h periods at baseline and on days 7 and 14 of a 14-day subcutaneous infusion of IL-1β (10 ng/h), IL-6 (16 ng/h), or vehicle. By day 14, plasma ET-1 was significantly increased by IL-1β infusion (1.7 ± 0.1 vs. 0.8 ± 0.1 pg/ml for vehicle, P < 0.001). Compared with vehicle infusion, IL-1β infusion induced significant increases in urinary ET-1 excretion rate and urine flow but did not affect conscious mean arterial pressure (telemetry). IL-1β infusion significantly increased renal cortical and medullary IL-1β content (ELISA) and prepro-ET-1 mRNA expression (quantitative real-time PCR). In contrast, 14 days of IL-6 infusion had no significant effect on plasma ET-1 or urinary ET-1 excretion rate. To determine whether IL-1β stimulates ET-1 release via activation of NF-κB, inner medullary collecting duct (IMCD-3) cells were incubated for 24 h with IL-1β, and ET-1 release and NF-κB activation were measured (ELISA). IL-1β activated NF-κB and increased ET-1 release in a concentration-dependent manner. The effect of IL-1β on ET-1 release could be partially inhibited by pretreatment of IMCD-3 cells with an inhibitor of NF-κB activation (BAY 11-7082). These results indicate that IL-1β stimulates renal and systemic ET-1 production in vivo, providing further evidence that ET-1 participates in inflammatory responses.

scholarly journals An integrated analysis of myeloid cells identifies gaps in in vitro models of in vivo biology

2019 ◽  
Author(s):  
Nadia Rajab ◽  
Paul W Angel ◽  
Yidi Deng ◽  
Jennifer Gu ◽  
Vanta Jameson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Myeloid Cell ◽  
Cell Types ◽  
In Vitro Models ◽  
Integrated Analysis ◽  
Dendritic Cell Subsets ◽  
Cell Data

SummaryThe Stemformatics myeloid atlas is an integrated transcriptome atlas of human macrophages and dendritic cells that systematically compares freshly isolated tissue-resident, cultured, and stem-cell derived myeloid cell types. We identified two broad classes of tissue-resident macrophages with lung, gut and tumour-associated macrophages most similar to monocytes. Microglia, Kupffer cells and synovial macrophages shared similar profiles with each other, and with cultured macrophages. Pluripotent stem cell-derived macrophages were not reminiscent of fetal-derived cells. Instead, they were characterized by atypical expression of collagen and a highly efferocytotic phenotype. Likewise, Flt3L-derived cord blood dendritic cells were distinct from conventional dendritic cell subsets isolated from primary tissues and lacked expression of key pattern recognition receptors. Myeloid subsets were reproducible across different experimental series, showing the resource is a robust reference for new data. External users can annotate and benchmark their own samples, including annotation of myeloid single cell data at www.stemformatics.org/atlas/myeloid/.

Eucalyptus globulus Inhibits Inflammasome-Activated Pro-Inflammatory Responses and Ameliorate Monosodium Urate-Induced Peritonitis in Murine Experimental Model

2018 ◽  
Vol 46 (02) ◽  
pp. 423-433 ◽  
Author(s):  
Young-Eun Ji ◽  
Xiao Sun ◽  
Myong-Ki Kim ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
...  
Keyword(s):  
Eucalyptus Globulus ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Monosodium Urate ◽  
Traditional Use ◽  
Folk Remedy

Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3926-3931 ◽  
Author(s):  
Renato Zambello ◽  
Tamara Berno ◽  
Giovanna Cannas ◽  
Ilenia Baesso ◽  
Gianni Binotto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Specific Antigen ◽  
Cell Types ◽  
Lymphoproliferative Disease ◽  
Topographic Organization ◽  
Functional Analyses ◽  
Granular Lymphocytes

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DCs, providing evidence for a role of DCs in the pathogenesis of LDGL.

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