scholarly journals Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alina S. Dzharullaeva ◽  
Amir I. Tukhvatulin ◽  
Alina S. Erokhova ◽  
Alina S. Bandelyuk ◽  
Nikita B. Polyakov ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Raw 264.7 Macrophages ◽  
Immune Reactions ◽  
Lectin Receptor ◽  
Effective Strategies ◽  
Parenteral Immunization

Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.

TECHNIQUES FOR ELICITING MUCOSAL IMMUNE RESPONSE

1975 ◽  
Vol 80 (2_Suppl) ◽  
pp. S262-S280 ◽  
Author(s):  
R. H. Waldman ◽  
R. Ganguly
Keyword(s):  
Immune Response ◽  
Antibody Formation ◽  
Antigen Processing ◽  
Large Body ◽  
Vaccine Dose ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Cell Mediated Immunity ◽  
Mucosal Surfaces ◽  
Parenteral Immunization

ABSTRACT Development of techniques for eliciting an immune response on mucosal surfaces is a relatively new area of clinical research. With the recognition of the existence of secretory immunity, independent of the systemic system, there was renewed interest in re-examining the conventional approach for optimal immunization techniques. A large body of data indicate that the majority of the secretory immunoglobulins and antibody produced to antigenic stimulation of mucosal surfaces is locally produced. Thus, antibody to C. albicans in the cervical or vaginal mucus has been shown to be of local origin and it predominantly belongs to the secretory IgA immunoglobulin class. The mechanism of antigen processing by the secretory surface leading to antibody formation remains a mystery, but it might be determined by the selective localization of antigens in the reticuloendothelial cells of the lamina propria, bronchi or small intestine. Usually application of antigen topically to the mucosal surface elicits local antibody formation to a greater extent than does parenteral immunization. On the other hand, a more pronounced systemic immune response is seen when the antigen is administered systemically. However, a number of other factors determine the quality and quantity of the immune response, e. g., the physical state of the antigen, live vs killed vaccine, dose, adjuvant, previous exposure to similar or cross-reacting antigens, and site of application of the antigen. These factors are discussed in the review. Recent observations suggest that cell mediated immunity is a component of the secretory immune system, and like the humoral mechanism, also may be partially compartmentalized.

scholarly journals Expression of the polymeric immunoglobulin receptor and excretion of secretory IgA in the postischemic kidney

1999 ◽  
Vol 276 (5) ◽  
pp. F666-F673 ◽  
Author(s):  
James C. Rice ◽  
Jeff S. Spence ◽  
Judit Megyesi ◽  
Randall M. Goldblum ◽  
Robert L. Safirstein
Keyword(s):  
Mucosal Immune Response ◽  
Secretory Component ◽  
Secretory Iga ◽  
Polymeric Immunoglobulin Receptor ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Immunoglobulin Receptor ◽  
Medullary Thick Ascending Limb ◽  
Tract Infections

The humoral mucosal immune response of the kidney involves the transport of secretory IgA (S-IgA) through renal epithelial cells by the polymeric immunoglobulin receptor (pIgR). The pIgR is cleaved and released as free secretory component (FSC) or attached to IgA (S-IgA). We examined the effects of an ischemic model of acute renal failure (ARF) on the expression of pIgR and the secretion of FSC and S-IgA in the urine. Kidney pIgR mRNA levels decreased in ischemic animals by 55% at 4 h and by 85% at 72 h compared with controls. pIgR protein expression in the medullary thick ascending limb (TAL) decreased within 24 h and was nearly undetectable by 72 h. Urinary S-IgA and FSC concentrations decreased by 60% between days 3 and 6. pIgR mRNA and pIgR protein in the kidney returned to ∼90% of control levels and urinary FSC and S-IgA concentrations returned to ∼55% of control levels by day 7. We demonstrate that ischemic ARF decreases renal mucosal S-IgA transport in vivo and may contribute to the increased incidence of urinary tract infections.

Activation of isolated heterophils from chicks stimulated in vivo with salmonella enteritidis-immune lymphokines

1996 ◽  
Vol 54 ◽  
pp. 760-761
Author(s):  
R. B. Moyes ◽  
R. E. Droleskey ◽  
M. H. Kogut ◽  
J. R. DeLoach
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Salmonella Enteritidis ◽  
Intestinal Tract ◽  
Polymorphonuclear Cells ◽  
Subclinical Infection ◽  
Egg Products ◽  
Immune Lymphokines ◽  
Organ Invasion

Salmonella enteritidis (SE) is of great concern to the poultry industry due to the organism's ability to penetrate the intestinal mucosa of the laying hen and subsequently colonize the ovaries and yolk membrane. The resultant subclinical infection can lead to SE infection of raw eggs and egg products. Interference with the ability of the organism to invade has been linked to the activation and recruitment of inflammatory polymorphonuclear cells, heterophils, to the lamina propria of the intestinal tract.Recently it has been established that heterophil activation and increased resistance to SE organ invasion can be accomplished by the administration of SE-immune lymphokines (SE-ILK) obtained from supernatants of concanavalin-A stimulated SE immune T lymphocytes from SE hyperimmunized hens. Invasion of SE into the lamina propria provides a secondary signal for directing activated heterophils to the site of SE invasion.

Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Mononuclear Cells ◽  
Multiple Organ ◽  
Peripheral Blood Mononuclear ◽  
Dornase Alfa ◽  
Tract Infections ◽  
Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

scholarly journals In Vitro and In Vivo Anti-Inflammatory Effects of Sulfated Polysaccharides Isolated from the Edible Brown Seaweed, Sargassum fulvellum

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 277
Author(s):  
Lei Wang ◽  
Hye-Won Yang ◽  
Ginnae Ahn ◽  
Xiaoting Fu ◽  
Jiachao Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brown Seaweed ◽  
Sulfated Polysaccharides ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Sargassum Fulvellum ◽  
Pharmaceutical Industries ◽  
Anti Inflammatory

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.

scholarly journals Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

2021 ◽  
Author(s):  
G. Amato ◽  
T. Saleh ◽  
G. Carpino ◽  
E. Gaudio ◽  
D. Alvaro ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Cell Delivery ◽  
Effective Strategies ◽  
Multiple Strategies ◽  
End Stage ◽  
Therapy Strategies ◽  
Injury Models ◽  
Experimental Liver

Abstract Purpose of Review To describe experimental liver injury models used in regenerative medicine, cell therapy strategies to repopulate damaged livers and the efficacy of liver bioengineering. Recent Findings Several animal models have been developed to study different liver conditions. Multiple strategies and modified protocols of cell delivery have been also reported. Furthermore, using bioengineered liver scaffolds has shown promising results that could help in generating a highly functional cell delivery system and/or a whole transplantable liver. Summary To optimize the most effective strategies for liver cell therapy, further studies are required to compare among the performed strategies in the literature and/or innovate a novel modifying technique to overcome the potential limitations. Coating of cells with polymers, decellularized scaffolds, or microbeads could be the most appropriate solution to improve cellular efficacy. Besides, overcoming the problems of liver bioengineering may offer a radical treatment for end-stage liver diseases.

Sign in / Sign up

Export Citation Format

Share Document