The Role of Innate Immunity and Bioactive Lipid Mediators in COVID-19 and Influenza.
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ABSTRACT:
SUBMITTER: Sahanic S
PROVIDER: S-EPMC8339726 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death.Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important.Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.
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Project description:Inflammatory activity is evident in patients with chronic kidney disease with limited data available in autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that inflammation is an upstream event in the pathogenesis of ADPKD and may be a contributing factor in the disease severity and progression. Serum samples from 61 HALT study A group patients were compared with samples from 49 patients from HALT study B group with moderately advanced disease. Targeted MS analysis of bioactive lipid mediators as markers of inflammation was performed and correlated with eGFR and total kidney volume (TKV) normalized to the body surface area (BSAR) to assess if these markers are predictive of ADPKD severity. ADPKD patients with eGFR >60 ml/min/1.73 m(2) showed higher levels of 5- and 12/15-lipoxygenase (LOX) and cyclooxygenase, and generated higher levels of hydroxy-octadecadienoic acids 9-HODE and 13-HODE and HETEs 8-HETE, 11-HETE, 12-HETE, and 15-HETE as compared with healthy subjects. Linear regression of 9-HODE and 13-HODE revealed a significant relationship with eGFR and TKV, while 15-HETE significantly correlated with TKV/BSAR. Production of 20-HETE, a P450-produced metabolite of arachidonic acid, was higher in ADPKD patients as compared with healthy subjects and significantly correlated with eGFR and TKV/BSAR. Perturbation in fatty acid metabolism is evident early in ADPKD patients, even in those with preserved kidney function. The identified LOX pathways may be potential therapeutic targets for slowing down ADPKD progression.
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Project description: Not available
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Project description:Virulent Mycobacterium tuberculosis (Mtb) induces a maladaptive cytolytic death modality, necrosis, which is advantageous for the pathogen. We report that necrosis of macrophages infected with the virulent Mtb strains H37Rv and Erdmann depends on predominant LXA(4) production that is part of the antiinflammatory and inflammation-resolving action induced by Mtb. Infection of macrophages with the avirulent H37Ra triggers production of high levels of the prostanoid PGE(2), which promotes protection against mitochondrial inner membrane perturbation and necrosis. In contrast to H37Ra infection, PGE(2) production is significantly reduced in H37Rv-infected macrophages. PGE(2) acts by engaging the PGE(2) receptor EP2, which induces cyclic AMP production and protein kinase A activation. To verify a role for PGE(2) in control of bacterial growth, we show that infection of prostaglandin E synthase (PGES)(-/-) macrophages in vitro with H37Rv resulted in significantly higher bacterial burden compared with wild-type macrophages. More importantly, PGES(-/-) mice harbor significantly higher Mtb lung burden 5 wk after low-dose aerosol infection with virulent Mtb. These in vitro and in vivo data indicate that PGE(2) plays a critical role in inhibition of Mtb replication.
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Project description:Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
2021-05-08 | GSE174072 | GEO
Project description:Recent advances in genome technologies have uncovered thousands of long non-coding RNAs (lncRNAs) whose function in the immune system has been largely unexplored. Members of the Toll-like receptor (TLR) family activate an inducible program of inflammatory genes important in host defenses. Here we provide evidence that TLRs induce the expression of many lncRNAs. One of these (lncRNA-Cox2) modulates the expression of hundreds of TLR2-inducible genes. Functional studies identified this lncRNA as capable of both activation and repression of distinct groups of TLR-induced genes. Transcriptional repression mediated by lncRNA-Cox2 requires heterogeneous ribonucleoprotein A/B and A2/B1, binding partners for lncRNA-Cox2. Collectively, these studies identify lncRNA-Cox2 as a broad-acting component of the regulatory circuit that controls the TLR-induced inflammatory response. Examination of Mus musculus (C57BL/6 background) gene exression changes following stimulation with Pam3Cys4 in presence or absence of shRNA specifically targetting lncRNA-COX2
2013-08-26 | E-GEOD-40978 | biostudies-arrayexpress
Project description:Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility. Author summary COVID-19, caused by the virus SARS-CoV-2, has claimed millions of lives and affected many more since its emergence. A number of studies have previously suggested that influenza vaccination can provide protection against COVID-19. Although multiple COVID-19 vaccines are currently available, emergence of new variants and inequity in vaccine distribution around the world make it crucial to identify alternative ways that can help in the fight against this pandemic. With this in mind, we investigated if seasonal influenza vaccination had any effect on COVID-19 incidence. Dutch healthcare workers who received the influenza vaccine in the previous flu season had 37% and 49% lower risk of SARS-CoV-2 infection in the first two waves of the pandemic, respectively. We also explored the mechanisms underlying this observation, using various techniques such as single-cell RNA sequencing, proteomics, and stimulation assays. The influenza vaccine reduced systemic inflammation and reprogrammed the immune cells to fine-tune the response against SARS-CoV-2. This study reveals influenza vaccination as a safe and helpful tool to decrease COVID-19 burden.
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Project description:SARS-CoV-2 infection associated respiratory disease- COVID-19 has evolved into a pandemic but, being a new form of virus, pathogenesis of disease causation is not fully understood and drugs and vaccines against this virus are still being tested so that no effective drugs or vaccines have been advised by regulatory authority. In this context, the Ministry of AYUSH, Government of India has recommended 'Ayush Kwath' to improve the immunity and combat the infection. Our objective of this literature review is to review the role of immunity in pathogenesis of COVID-19 and role of Ayush Kwath against the virus and regulation of immunity. Current review was conducted using a search of available literature on COVID-19 and immunity, Vyadhikshamatwa, Ayurveda and COVID-19, Rasayana, Coronavirus, SARS-CoV-2, immunomodulatory effects of medicinal plants; Tulsi/Holy Basil/Ocimum sanctum, Dalchini/Cinnamon/Cinnamomum zeylanicum, Sunthi/Ginger/Zingiber officinale and Marich/Black Pepper/Piper nigrum. Ayurveda, being an ancient science have both medicinal and cultural values and had stimulated our kitchen and influenced what we ate in different seasons and the remedies we used for common ailments. Herbs such as Tulsi, Marich, Sunthi, Dalchini are the most commonly used and easily available drugs in home. Thus, Ayush Kwath due to its immune-modulatory, antiviral, anti-oxidant, anti-inflammatory, anti-platelet, anti-atherosclerotic, hepato-protective, reno-protective properties; seems to be effective in immuno-regulation for controlling viral infections like COVID-19. Further pre-clinical and clinical trials need to be done for the evaluation of safety and efficacy of this polyherbal formulation.
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Project description:Majority of patients infected with the COVID 19 virus display a mild to moderate course of disease and spontaneously recover at 14-20 days. However, about 15% of patients progress to severe stages and 2.5% of these patients succumb to this illness. Most patients with severe disease belong to the elderly age group (<65 years of age) and have multiple associated co-morbidities. The immune responses induced by the COVID 19 virus, during the incubation and non-severe stages, requires the early initiation of a specific adaptive immune response to eliminate the virus and prevent the progress to severe stages. In patients with a dysfunctional bridge adaptive immunity, the innate immune response becomes exaggerated due to the lack of feedback from the adaptive immune cells. The resultant cytokine storm is responsible for the severe lung injury leading to acute respiratory distress syndrome seen in COVID 19 patients. Mesenchymal stem cells are known to suppress overactive immune responses as well as bring about tissue regeneration and repair. This immuno-modulatory effect of MSCs could hold potential to manage a patient with severe symptoms of COVID 19 infection due to a dysfunctional adaptive immune system.
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Project description:Placozoa is a phylum of non-bilaterian marine animals. These small, flat organisms adhere to the substrate via their densely ciliated ventral epithelium, which mediates mucociliary locomotion and nutrient uptake. They have only six morphological cell types, including one, fiber cells, for which functional data is lacking. Fiber cells are non-epithelial cells with multiple processes. We used electron and light microscopic approaches to unravel the roles of fiber cells in Trichoplax adhaerens, a representative member of the phylum. Three-dimensional reconstructions of serial sections of Trichoplax showed that each fiber cell is in contact with several other cells. Examination of fiber cells in thin sections and observations of live dissociated fiber cells demonstrated that they phagocytose cell debris and bacteria. In situ hybridization confirmed that fiber cells express genes involved in phagocytic activity. Fiber cells also are involved in wound healing as evidenced from microsurgery experiments. Based on these observations we conclude that fiber cells are multi-purpose macrophage-like cells. Macrophage-like cells have been described in Porifera, Ctenophora, and Cnidaria and are widespread among Bilateria, but our study is the first to show that Placozoa possesses this cell type. The phylogenetic distribution of macrophage-like cells suggests that they appeared early in metazoan evolution.
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