scholarly journals Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and enhance immunity

2021 ◽  
Author(s):  
Evgeniya V Shmeleva ◽  
Mercedes Gomez de Agüero ◽  
Josef Wagner ◽  
Anton J Enright ◽  
Andrew J Macpherson ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Inflammatory Cells ◽  
Smallpox Vaccination ◽  
Intradermal Vaccination ◽  
Live Vaccines ◽  
T Cell Infiltration ◽  
Cytokines And Chemokines ◽  
Skin Bacteria ◽  
Specific Pathogen ◽  
Inflammatory Tissue

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20 th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and increase immunity. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF mice had reduced VACV-neutralising antibodies compared to SPF mice; while numbers of VACV-specific CD8 + T cells were equal in all groups of animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV. This observation has implications for dermal vaccination with live vaccines.

scholarly journals Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisuke Morichika ◽  
Akihiko Taniguchi ◽  
Naohiro Oda ◽  
Utako Fujii ◽  
Satoru Senoo ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Cigarette Smoke Extract ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Porcine Pancreas ◽  
Obstructive Pulmonary Disease ◽  
Quantitative Morphometry ◽  
Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

scholarly journals Overlapping Roles for Interleukin-36 Cytokines in Protective Host Defense against MurineLegionella pneumophilaPneumonia

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Yuta Nanjo ◽  
Michael W. Newstead ◽  
Tetsuji Aoyagi ◽  
Xianying Zeng ◽  
Kazuhisa Takahashi ◽  
...  
Keyword(s):  
Host Defense ◽  
Legionella Pneumophila ◽  
Ex Vivo ◽  
Inflammatory Cells ◽  
Bacterial Clearance ◽  
Content Type ◽  
Cytokines And Chemokines ◽  
M1 Polarization ◽  
Life Threatening ◽  
Deficient Mice

ABSTRACTLegionella pneumophilacauses life-threatening pneumonia culminating in acute lung injury. Innate and adaptive cytokines play an important role in host defense againstL. pneumophilainfection. Interleukin-36 (IL-36) cytokines are recently described members of the larger IL-1 cytokine family known to exert potent inflammatory effects. In this study, we elucidated the role for IL-36 cytokines in experimental pneumonia caused byL. pneumophila. Intratracheal (i.t.) administration ofL. pneumophilainduced the upregulation of both IL-36α and IL-36γ mRNA and protein production in the lung. Compared to the findings forL. pneumophila-infected wild-type (WT) mice, the i.t. administration ofL. pneumophilato IL-36 receptor-deficient (IL-36R−/−) mice resulted in increased mortality, a delay in lung bacterial clearance, increasedL. pneumophiladissemination to extrapulmonary organs, and impaired glucose homeostasis. Impaired lung bacterial clearance in IL-36R−/−mice was associated with a significantly reduced accumulation of inflammatory cells and the decreased production of proinflammatory cytokines and chemokines.Ex vivo, reduced expression of costimulatory molecules and impaired M1 polarization were observed in alveolar macrophages isolated from infected IL-36R−/−mice compared to macrophages from WT mice. WhileL. pneumophila-induced mortality in IL-36α- or IL-36γ-deficient mice was not different from that in WT animals, antibody-mediated neutralization of IL-36γ in IL-36α−/−mice resulted in mortality similar to that observed in IL-36R−/−mice, indicating redundant and overlapping roles for these cytokines in experimental murineL. pneumophilapneumonia.

Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione

2009 ◽  
Vol 425 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Valdecir F. Ximenes ◽  
Ghassan J. Maghzal ◽  
Rufus Turner ◽  
Yoji Kato ◽  
Christine C. Winterbourn ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Tissue Damage ◽  
Acid Production ◽  
Hypochlorous Acid ◽  
Human Neutrophils ◽  
Toxic Metabolite ◽  
Inflammatory Processes ◽  
Physiological Substrates ◽  
Inflammatory Tissue

During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

scholarly journals Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain

Gut ◽  
1998 ◽  
Vol 43 (1) ◽  
pp. 71-78 ◽  
Author(s):  
S Matsumoto ◽  
Y Okabe ◽  
H Setoyama ◽  
K Takayama ◽  
J Ohtsuka ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Cells ◽  
Intestinal Wall ◽  
Human Inflammatory Bowel Disease ◽  
Specific Pathogen ◽  
Inflammatory Bowel ◽  
Oxide Synthase ◽  
Senescence Accelerated Mouse ◽  
Inducible Nitric Oxide

Background—A new subline of the senescence accelerated mouse (SAM) P1/Yit strain has been established which shows spontaneous enteric inflammation under specific pathogen free (SPF) conditions.Aims—To elucidate the pathogenesis of enteric inflammation in this new subline.Methods—The SPF and germ free (GF) SAMP1/Yit strains were used. Histological, immunological, and microbiological characterisation of the mice with enteric inflammation was performed.Results—Histologically, enteritic inflammation developed as a discontinuous lesion in the terminal ileum and caecum with the infiltration of many inflammatory cells after 10 weeks of age. The activity of myeloperoxidase, and both immunolocalisation and mRNA expression of inducible nitric oxide synthase increased in the lesion. CD3-ε positive T cells, neutrophils, and macrophages were more numerous in the inflamed mucosa of the SAMP1/Yit strain. The GF SAMP1/Yit strain did not show any inflammation in the intestinal wall, by the age of 30 weeks, and the enteritis and caecitis developed 10 weeks after the conventionalisation of the GF SAMP1/Yit strain.Conclusion—Enteric inflammation in the ileum and caecum developed in the SAMP1/Yit strain. The pathophysiological characteristics of the disease in this mouse have some similarities to those of human inflammatory bowel disease (IBD). This mouse strain should be a useful model system for elucidating the interaction between the pathogenesis of IBD and the gut microflora.

scholarly journals Effect of Antibiotics on the Colonization of Live Attenuated Salmonella Enteritidis Vaccine in Chickens

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiangang Hu ◽  
Chuanyan Che ◽  
Jiakun Zuo ◽  
Xiangpeng Niu ◽  
Zhihao Wang ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enteritidis ◽  
Antibiotic Use ◽  
Live Vaccine ◽  
Live Vaccine Strain ◽  
Specific Pathogen Free ◽  
Live Vaccines ◽  
The World ◽  
Specific Pathogen ◽  
Effective Use

Salmonellosis, caused by Salmonella Enteritidis, is a prevalent zoonosis that has serious consequences for human health and the development of the poultry sector. The Salmonella Enteritis live vaccine (Sm24/Rif12/Ssq strain) is used to prevent Salmonella Enteritidis around the world. However, in some parts of the world, poultry flocks are frequently raised under intensive conditions, with significant amounts of antimicrobials to prevent and treat disease and to promote growth. To investigate whether antibiotic use influences the colonization of orally administered Salmonella live vaccines, 240 1-day-old specific pathogen-free chicks were randomly divided into 24 groups of 10 animals for this study. The different groups were treated with different antibiotics, which included ceftiofur, amoxicillin, enrofloxacin, and lincomycin–spectinomycin. Each group was immunized 2, 3, 4, and 5 days after withdrawal, respectively. At 5 days after immunization, the blood, liver, and ceca with contents were collected for the isolation of the Salmonella live vaccine strain. The result showed that no Salmonella vaccine strain was isolated in the blood and liver of the chicks in those groups. The highest number of Salmonella vaccine strains was isolated in the cecum from chicks vaccinated 2 days after ceftiofur withdrawal, and no Salmonella vaccine strain was isolated from the cecum in chicks immunized 3 days after ceftiofur withdrawal. Among the chickens immunized 4 days after the withdrawal of amoxicillin, enrofloxacin, and lincomycin–spectinomycin, the number of Salmonella vaccine colonization in the cecum was the highest, which was higher than that of the chickens immunized at other withdrawal interval (2, 3, and 5 days) groups and was higher than that of the chickens without treatment (P < 0.05). This study provides a reference for the effective use of the Salmonella Enteritidis live vaccine and key antibiotics commonly utilized in the poultry industry.

scholarly journals Extracellular vesicles from mature dendritic cells (DC) differentiate monocytes into immature DC

2018 ◽  
Vol 1 (6) ◽  
pp. e201800093 ◽  
Author(s):  
Stefan Schierer ◽  
Christian Ostalecki ◽  
Elisabeth Zinser ◽  
Ricarda Lamprecht ◽  
Bianca Plosnita ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Extracellular Vesicles ◽  
Immune Reaction ◽  
Immune Cell ◽  
Mouse Skin ◽  
Inflammatory Cells ◽  
Activation Markers ◽  
Gm Csf ◽  
Cytokines And Chemokines ◽  
Maturation Stimulus

During inflammation, murine and human monocytes can develop into dendritic cells (DC), but this process is not entirely understood. Here, we demonstrate that extracellular vesicles (EV) secreted by mature human DC (maDC) differentiate peripheral monocytes into immature DC, expressing a unique marker pattern, including 6-sulfo LacNAc (slan), Zbtb46, CD64, and CD14. While EV from both maDC and immature DC differentiated monocytes similar to GM-CSF/IL-4 stimulation, only maDC-EV produced precursors, which upon maturation stimulus developed into T-cell–activating and IL-12p70–secreting maDC. Mechanistically, maDC-EV induced cell signaling through GM-CSF, which was abundant in EV as were IL-4 and other cytokines and chemokines. When injected into the mouse skin, murine maDC-EV attracted immune cells including monocytes that developed activation markers typical for inflammatory cells. Skin-injected EV also reached lymph nodes, causing a similar immune cell infiltration. We conclude that DC-derived EV likely serve to perpetuate an immune reaction and may contribute to chronic inflammation.

scholarly journals A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir vs Currently Used Therapy in Severe COVID-19 Adults. “COMVIVIR” Trial.

2020 ◽  
Author(s):  
Adolfo Pérez-García ◽  
Alma Villalobos-Osnaya ◽  
Maria Luisa Hernández-Medel ◽  
Lucia Monserrat Perez-Navarro ◽  
Elba O. Medina-Hernandez ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Antiviral Drug ◽  
Inflammatory Cells ◽  
Current Treatment ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Cytokines And Chemokines ◽  
Cytokine Dysregulation ◽  
Hospital General

Abstract Multiple studies have established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of T cells, monocytes/macrophages and neutrophils, thus mitigating the cytokine dysregulation and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients should combine a modulator of the immune response plus a direct antiviral drug against SARS-CoV-2, in order to address both the hyperinflammatory effects of the immune dysregulation and the viral load. Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México Dr. Eduardo Liceaga for severe COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groups. Discussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-β; nevertheless, to our best knowledge, only one study explores chemotaxis control. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomes.

scholarly journals A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir vs Currently Used Therapy in Severe COVID-19 Adults. “COMVIVIR” Trial.

2020 ◽  
Author(s):  
Adolfo Pérez-García ◽  
Alma Villalobos-Osnaya ◽  
Maria Luisa Hernández-Medel ◽  
Lucia Monserrat Perez-Navarro ◽  
Elba O. Medina-Hernandez ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Antiviral Drug ◽  
Inflammatory Cells ◽  
Current Treatment ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Cytokines And Chemokines ◽  
Cytokine Dysregulation ◽  
Hospital General

Abstract Multiple studies have established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of T cells, monocytes/macrophages and neutrophils, thus mitigating the cytokine dysregulation and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients should combine a modulator of the immune response plus a direct antiviral drug against SARS-CoV-2, in order to address both the hyperinflammatory effects of the immune dysregulation and the viral load. Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México Dr. Eduardo Liceaga for severe COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groups. Discussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-β; nevertheless, to our best knowledge, only one study explores chemotaxis control. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomes.

Oxidative stress and its implications in chronic kidney disease

2015 ◽  
Author(s):  
Nosratola D. Vaziri
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tissue Damage ◽  
Oxygen Radicals ◽  
Inflammatory Cells ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Low Levels

Reactive oxygen species (ROS) are produced at low levels physiologically and their production conveys signals and has specific functions. Control mechanisms ensure that this does not cause damage. ROS are highly reactive and cytotoxic and are also deliberately produced by inflammatory cells (granulocytes, macrophages) to kill pathogens. If these chemicals are released inappropriately or excessively, or if control mechanisms are under-functioning, bystander or unintended tissue damage may be caused. The concept of oxidative stress is based on the idea that in certain states, commonly inflammatory states, release of oxygen radicals may be excessive, or control mechanisms weakened, so that tissue damage occurs. In CKD, both overproduction and diminished control may apply. No effective therapies acting via these pathways have been established so far though there remain some candidates.

scholarly journals The Role of Mesenchymal Stem Cells in Atherosclerosis: Prospects for Therapy via the Modulation of Inflammatory Milieu

2019 ◽  
Vol 8 (9) ◽  
pp. 1413 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Maciej Banach ◽  
Željko Reiner ◽  
Matteo Pirro ◽  
Saeideh Hajighasemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Strategies ◽  
Plasma Lipid ◽  
Inflammatory Cells ◽  
Chronic Inflammatory Disease ◽  
The Body ◽  
Older Individuals ◽  
Cytokines And Chemokines ◽  
Novel Strategy

Atherosclerosis is a chronic, inflammatory disease that mainly affects the arterial intima. The disease is more prevalent in middle-age and older individuals with one or more cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, smoking, obesity, and others. The beginning and development of atherosclerosis has been associated with several immune components, including infiltration of inflammatory cells, monocyte/macrophage-derived foam cells, and inflammatory cytokines and chemokines. Mesenchymal stem cells (MSCs) originate from several tissue sources of the body and have self-renewal and multipotent differentiation characteristics. They also have immunomodulatory and anti-inflammatory properties. Recently, it was shown that MSCs have a regulatory role in plasma lipid levels. In addition, MSCs have shown to have promising potential in terms of treatment strategies for several diseases, including those with an inflammatory component. In this regard, transplantation of MSCs to patients with atherosclerosis has been proposed as a novel strategy in the treatment of this disease. In this review, we summarize the current advancements regarding MSCs for the treatment of atherosclerosis.

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