Immune System Inflammatory Response Research Articles

Conceptual Model of Sepsis as a Dysregulated Host Response: Depicting Directionality of Immunologic and Metabolic Dysregulation.

Background Mortality from Sepsis continues to remain high in hospitalized patients worldwide. Previously, the conceptual model of sepsis was based on the systemic inflammatory immune response syndrome, an adaptive model. In 2016, a new definition of sepsis was proposed as a dysregulated host response to infection, however until now, no model has been proposed elucidating what immunologic mechanisms are dysregulated. Aim We sought to propose a new model of sepsis to elucidate evidence-based immunologic and metabolic mechanisms which are dysregulated in sepsis. Methods Evidence in the literature comparing and contrasting sepsis before and after the 2016 consensus definition of sepsis was reviewed for themes. Themes from research published post 2016, were described connecting immunologic and metabolic mechanisms in sepsis. This information further informed earlier research that has been published by the primary author. Results A new conceptual model of sepsis was developed to elucidate the current definition of sepsis as a dysregulated host response, incorporating themes uncovered in sepsis research post 2016. Conclusion The model proposed here supports clinicians in applying the current definition of sepsis to a physiological model. This can benefit clinicians by offering new ways of recognizing sepsis, and researchers by recommending a physiologic model to advance sepsis research. Keywords: Sepsis, sepsis model, immunologic dysregulation, metabolic dysregulation

Possible Effects of Inflammation by Covid-19 on the Human Brain

The immune system's inflammatory response is a crucial defense mechanism against infectious agents. At the onset of the pandemic, researchers primarily focused on the respiratory consequences of coronavirus, while overlooking the virus's impact on other organs, such as the brain. However, it is now apparent that post-covid sequelae can persist, especially in those who suffered severe forms of the disease. These symptoms include memory impairment, excessive fatigue, and mood swings. This study examines the possible link between the brain's inflammatory response and these prevalent sequelae, as well as strategies to improve the quality of life for those affected.

Microbiome and physical activity.

Regular physical activity promotes health benefits and contributes to develop the individual biological potential. Chronical physical activity performed at moderate and high-intensity is the intensity more favorable to produce health development in athletes and improve the gut microbiota balance. The athletic microbiome is characterized by increased microbial diversity and abundance as well as greater phenotypic versatility. In addition, physical activity and microbiota composition have bidirectional effects, with regular physical activity improving microbial composition and microbial composition enhancing physical performance. The improvement of physical performance by a healthy microbiota is related to different phenotypes: i) efficient metabolic development, ii) improved regulation of intestinal permeability, iii) favourable modulation of local and systemic inflammatory and efficient immune responses, iv) efective regulation of systemic pH and, v) protection against acute stressful events such as environmental exposure to altitude or heat. The type of sport, both intensity or volume characteristics promote microbiota specialisation. Individual assessment of the state of the gut microbiota can be an effective biomarker for monitoring health in the medium to long term. The relationship between the microbiota and the rest of the body is bidirectional and symbiotic, with a full connection between the systemic functions of the nervous, musculoskeletal, endocrine, metabolic, acid-base and immune systems. In addition, circadian rhythms, including regular physical activity, directly influence the adaptive response of the microbiota. In conclusion, regular stimuli of moderate- and high-intensity physical activity promote greater diversity, abundance, resilience and versatility of the gut microbiota. This effect is highly beneficial for human health when healthy lifestyle habits including nutrition, hydration, rest, chronoregulation and physical activity.

Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies.

Cardiovascular diseases (CVDs) identified as a serious public health problem. Although there is a lot of evidence that inflammatory processes play a significant role in the progression of CVDs, however, the precise mechanism is not fully understood. Nevertheless, recent studies have focused on inflammation and its related agents. Nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) is a type of pattern recognition receptor (PRR) that can recognize pathogen-associated molecular patterns and trigger innate immune response. NLRP3 is a component of the NOD-like receptor (NLR) family and have a pivotal role in detecting damage to cardiovascular tissue. It is suggested that activation of NLRP3 inflammasome leads to initiating and propagating the inflammatory response in cardiomyopathy. So, late investigations have highlighted the NLRP3 inflammasome activation in various forms of cardiomyopathy. On the other side, it was shown that noncoding RNAs (ncRNAs), particularly, microRNAs, lncRNAs, and circRNAs possess a regulatory function in the immune system's inflammatory response, implicating their involvement in various inflammatory disorders. In addition, their role in different cardiomyopathies was indicated in recent studies. This review article provides a summary of recent advancements focusing on the function of the NLRP3 inflammasome in common CVDs, especially cardiomyopathy, while also discussing the therapeutic potential of inhibiting the NLRP3 inflammasome regulated by ncRNAs.

NAD+ Metabolism and Immune Regulation: New Approaches to Inflammatory Bowel Disease Therapies.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial systemic inflammatory immune response. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme involved in cell signaling and energy metabolism. Calcium homeostasis, gene transcription, DNA repair, and cell communication involve NAD+ and its degradation products. There is a growing recognition of the intricate relationship between inflammatory diseases and NAD+ metabolism. In the case of IBD, the maintenance of intestinal homeostasis relies on a delicate balance between NAD+ biosynthesis and consumption. Consequently, therapeutics designed to target the NAD+ pathway are promising for the management of IBD. This review discusses the metabolic and immunoregulatory processes of NAD+ in IBD to examine the molecular biology and pathophysiology of the immune regulation of IBD and to provide evidence and theoretical support for the clinical use of NAD+ in IBD.

The role of the gut microbiome and its metabolites in cerebrovascular diseases.

The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.

The Microbiota-Gut-Brain Axis: Psychoneuroimmunological Insights.

There is growing interest in the role that the intestinal microbiota and the related autoimmune processes may have in the genesis and presentation of some psychiatric diseases. An alteration in the communication of the microbiota-gut-brain axis, which constitutes a communicative model between the central nervous system (CNS) and the gastro-enteric tract, has been identified as one of the possible causes of some psychiatric diseases. The purpose of this narrative review is to describe evidence supporting a role of the gut microbiota in psychiatric diseases and the impact of diet on microbiota and mental health. Change in the composition of the gut microbiota could determine an increase in the permeability of the intestinal barrier, leading to a cytokine storm. This could trigger a systemic inflammatory activation and immune response: this series of events could have repercussions on the release of some neurotransmitters, altering the activity of the hypothalamic-pituitary-adrenal axis, and reducing the presence of trophic brain factors. Although gut microbiota and psychiatric disorders seem to be connected, more effort is needed to understand the potential causative mechanisms underlying the interactions between these systems.

Integrated Analysis of Transcriptome in Interleukin-10 Treated Peripheral Blood Cell Reveal Conservative Differential Expressed Genes

Interleukin 10 is one of the important cytokines of immune system inflammatory response in critical diseases such as sepsis. The regulation mechanism of its signal pathway and the mining of key members can provide targets for disease diagnosis and treatment. A large number of studies have analyzed the response of interleukin 10 treated cells by means of transcriptome and identified the members of signal pathway from differentially expressed genes. However, the conditions of different studies are different, resulting in great differences in results. It is necessary to integrate and analyze the inherent differentially expressed genes. In this study, we collected 17 sets of transcriptome experimental results, all of which were analyzed in the treatment of interleukin 10 in peripheral blood cells. Through meta-analysis of 4695 gene expression in all experiments, we screened 134 genes, which were statistically significant differentially expressed genes in the random effect model (p<0.005). These genes enrich biological pathways related to immunity and wounding. Among them, the p value of tissue inhibitor of metalloproteinase 1, leupaxin, FAM20A Golgi associated secretory pathway pseudo kinase and interferon induced protein 44 is ≤9.82e-06. In 17 groups of experiments, the difference trend is relatively consistent and more experiments have detected more than twice the difference. These genes are valuable biomarkers for interleukin 10 related diseases such as sepsis. At the same time, it is a key member of the relatively more conservative interleukin 10 signaling pathway under different conditions.

Guanmaitong Granule Attenuates Atherosclerosis by Inhibiting Inflammatory Immune Response in ApoE-/- Mice Fed High-Fat Diet.

BackgroundAtherosclerosis (AS) is the leading cause of cardiovascular diseases, such as myocardial infarction and stroke. Guanmaitong granule (GMTG) is a TCM (Traditional Chinese medicine) prescribed to treat AS. However, its mechanism remains unclear.MethodsWe obtained reliable ingredients and targets of GMTG using the HERB database. AS-related targets were obtained from HERB and GeneCards databases. The target database was constructed by intersecting the ingredients of GMTG with the AS-related targets. STRING and Cytoscape were used to create protein-protein interaction (PPI) network and screen core targets. GO enrichment analysis and KEGG pathway analyses were performed using R. Finally, the ApoE−/− mice AS model was induced by a high-fat diet (HFD) for in vivo validation of core pathways and targets.ResultsA total of 124 ingredients and 418 potential targets of GMTG for treating AS were obtained. Numerous ingredients and targets were related to Panax notoginseng, Salvia miltiorrhiza, and Astragalus. Most core targets and pathways were involved in the inflammatory immune response. GMTG could decrease serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and oxidized low-density lipoprotein level and increase the serum high-density lipoprotein-cholesterol level. Furthermore, GMTG reduced the plaque burden and promoted plaque remodeling by reducing plaque area, lipid deposition, foam cell content, and collagen fiber content in the plaque in the aortic root of ApoE−/− mice. GMTG inhibited systemic and plaque inflammatory immune response and increased plaque stability by inhibiting the excessive release of the TLR4/MyD88/NF-κB pathway-induced inflammatory cytokines, tumor necrosis factor, interleukin-6, and interleukin-1 beta.ConclusionRadix notoginseng, Radix salviae liguliobae, and Radix astragali are the main ingredients of GMTG for treating AS. Further, GMTG could regulate the level of serum lipids and inhibit inflammatory immune response, which resulted in anti-AS effects such as plaque stabilization, reduction of plaque burden, and plaque remodeling. GMTG is a promising multi-target treatment for AS.

Citation: Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with Colitis in Mice.

A leaky gut is closely connected with systemic inflammation and psychiatric disorder. The rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induces gut inflammation and cognitive function in mice. Therefore, we selected Bifidobacterium longum NK219, Lactococcus lactis NK209, and Lactobacillus rhamnosus NK210, which induced claudin-1 expression in TNBS- or lipopolysaccharide (LPS)-stimulated Caco-2 cells, from the fecal bacteria collection of humans and investigated their effects on cognitive function and systemic inflammatory immune response in TNBS-treated mice. The intrarectal injection of TNBS increased cognitive impairment-like behaviors in the novel object recognition and Y-maze tests, TNF-α, IL-1β, and IL-17 expression in the hippocampus and colon, and LPS level in the blood and feces, while the expression of hippocampal claudin-5 and colonic claudin-1 decreased. Oral administration of NK209, NK210, and NK219 singly or together decreased TNBS-impaired cognitive behaviors, TNF-α and IL-1β expression, NF-κB+Iba1+ cell and LPS+Iba1+ cell numbers in the hippocampus, and LPS level in the blood and feces, whereas BDNF+NeuN+ cell and claudin-5+ cell numbers and IL-10 expression increased. Furthermore, they suppressed TNBS-induced colon shortening and colonic TNF-α and IL-1β expression, while colonic IL-10 expression and mucin protein-2+ cell and claudin-1+ cell numbers expression increased. Of these, NK219 most strongly alleviated cognitive impairment and colitis. They additively alleviated cognitive impairment with colitis. Based on these findings, NK209, NK210, NK219, and their combinations may alleviate cognitive impairment with systemic inflammation by suppressing the absorption of gut bacterial products including LPS into the blood through the suppression of gut bacterial LPS production and alleviation of a leaky gut by increasing gut tight junction proteins and mucin-2 expression.

Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.

ObjectiveSince the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization.MethodsTo achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression.ResultsEnriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion.ConclusionsOur findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.

Treatment of Crohn’s disease in children with adalimumab after being infected with SARS-CoV-2 at Children’s Hospital No. 2: a case report

Covid-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may lead to a severe inflammatory response or cytokine storm. Immune dysfunction in untreated Crohn’s disease may augment the risk for a severe inflammatory response to Covid-19. It is estimated that about 2% of severe children need to be hospitalised and the mortality rate is about 0.08%. Crohn’s disease most commonly occurs in the small intestine and the colon. It can affect any part of the gastrointestinal (GI) tract, from the mouth to the anus. Crohn’s patients on immunosuppressive medical therapy may encounter an increased SARS-CoV-2 infection risk. By contrast, immunosuppressive therapy may also have a potential benefit on clinical outcomes in Covid-19, since it may suppress not only mucosal inflammation but also the severe acute respiratory syndrome SARS-CoV-2-driven systemic inflammatory immune response. Adalimumab therapy can effectively treat both pediatric Crohn’s disease and multisystem inflammatory syndrome in children temporally associated with coronavirus disease 2019 infection. However, the management and follow-up plan still needs more consensus because it almost depends on steroids, adalimumab, and other drugs. Covid-19 in patients with Crohn’s disease has not been well documented in the literature. Therefore, in this study, the authors reported a case of a pediatric Crohn’s disease successfully treated with adalimumab after infected coronavirus 2 at Children’s Hospital No. 2 from September 7, 2021 to November 4, 2021.

Post-COVID-19 Condition: Where Are We Now?

COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.

INVESTIGATION OF THE RELATIONSHIP BETWEEN NEUTROPHIL/LYMPHOCYTE RATIO AND ANALGESIC CONSUMPTION IN BIMAXILLARY ORTHOGNATHIC SURGERY PATIENTS

Objectives Neutrophil to lymphocyte ratio; as an inexpensive, easily measurable, and repeatable laboratory parameter is an indicator of subclinical inflammation, and is also a parameter that gives an idea about the systemic inflammatory response and cellular immune response. In general, lymphopenia reflects the weakness of cellular immunity, while neutrophilia is indicative of the response to systemic inflammation. The ratio of these two values to each other seems to be a marker showing the adequacy of the cellular immune response against this situation, despite the magnitude of systemic inflammation. In this study, we aimed to investigate the relationship between preoperative neutrophil-lymphocyte ratio (NLR) and postoperative analgesic drug consumption. Materials and Method Within the scope of the study, the files of 50 patients who underwent bimaxillary orthognathic surgery were retrospectively analyzed. The preoperative NLR values of the patients and the need for the analgesic drugs in the first 24 hours and after 24 hours were recorded and correlated. Results 24% of the patients were girls and 76% were boys. The average age was 20.54, and the average weight was 65.28 kg. There was a positive, strong, and significant correlation between the preoperative neutrophil count and preoperative NLR value and variables of analgesic drug consumption in the first 24 hours (r = 0.6814, p &amp;lt;0.001, and r = 0.6148, p &amp;lt;0.001, respectively). There was a negative, strong and significant correlation between the preoperative lymphocyte count and the first 24-hour analgesic drug consumption variables (r = -0.6773, p &amp;lt;0.001). Conclusion It was concluded that patients with a preoperative NLR value of 2.11 and above may require 4 or more analgesics in the first 24 hours, therefore, NLR value can give preliminary information about the need for postoperative analgesia, and these values could be taken into account when developing a strategy for postoperative analgesia.

Pathophysiological Advantages of Spontaneous Ventilation.

Surgical procedures cause stress, which can induce an inflammatory response and reduce immune function. Following video-assisted thoracoscopic surgery (VATS), non-intubated thoracic surgery (NITS) was developed to further reduce surgical stress in thoracic surgical procedures. This article reviews the pathophysiology of the NITS procedure and its potential for reducing the negative effects of mechanical one-lung ventilation (mOLV). In NITS with spontaneous ventilation, the negative side effects of mOLV are prevented or reduced, including volutrauma, biotrauma, systemic inflammatory immune responses, and compensatory anti-inflammatory immune responses. The pro-inflammatory and anti-inflammatory cytokines released from accumulated macrophages and neutrophils result in injury to the alveoli during mOLV. The inflammatory response is lower in NITS than in relaxed-surgery cases, causing a less-negative effect on immune function. The increase in leukocyte number and decrease in lymphocyte number are more moderate in NITS than in relaxed-surgery cases. The ventilation/perfusion match is better in spontaneous one-lung ventilation than in mOLV, resulting in better oxygenation and cardiac output. The direct effect of relaxant drugs on the acetylcholine receptors of macrophages can cause cytokine release, which is lower in NITS. The locoregional anesthesia in NITS is associated with a reduced cytokine release, contributing to a more physiological postoperative immune function.

Is Immunosuppression a Risk Factor for Development of Peri-implantitis? A Retrospective Cohort Analysis

The present study aims to identify if immunosuppression is a risk factor for the development of peri-implantitis. A retrospective cohort study design was conducted on patients presenting to the Philadelphia Veterans Affairs (VA) Medical Center for dental implant placement from 2006 to 2013. Medical encounter notes within 3 months of implant placement were used to collect information about patients’ health status, including evaluations of immune system function. Implant status was assessed using dental encounter notes and radiographs from follow-up appointments at 1, 3, 5, and 10 years. Peri-implantitis was defined as radiographic evidence of change in crestal bone level, clinical evidence of bleeding on probing, with or without suppuration.1Electronic medical records of 884 implants were retrospectively analyzed. Descriptive statistics were calculated using the SAS System (SAS Institute Version 9.4, 2002-2012, Cary, NC). The primary predictor variable was immunosuppression. The primary outcome variable was the presence of peri-implantitis. Other study variables assessed included graft at the time of implant placement, diabetes, smoking, gender, and age over 60. Descriptive, univariate, and multivariate regression analyses were performed to measure the association between predictive variables and development of peri-implantitis.Of the 884 implants placed, 205 (23.1%) developed peri-implantitis. Following a multivariate analysis that controlled for diabetes, smoking, gender, and age over 60, immunosuppression was shown to be significantly associated with an increased risk in the presence of peri-implantitis (P = .0071) when compared to implants placed in immunocompetent subjects. The data from this study show that implants placed in immunosuppressed patients were 29.78% more likely to develop peri-implantitis compared to implants placed in immunocompetent patients (OR = 2.229, 95% CI 1.243-3.996). To the best of the authors’ knowledge, no existing literature has demonstrated this significant risk relationship.Following surgical implant placement, adequate function of the immune system's inflammatory response is imperative to target infections and orchestrates wound healing to allow for successful osseointegration of implants. Few studies, however, have directly investigated this nexus at a mechanistic level. In vivo studies in rabbits have indicated that titanium implant placement may up-regulate the immune system's type 2 inflammatory response to inhibit bone resorption markers and promote healing.2 Therefore, in conjunction with the authors' results, immunosuppression could play a significant role in increasing risk of peri-implantitis.Analysis of implants placed at the Philadelphia VA Medical Center revealed an important association between immunosuppression and the development of peri-implantitis. This study shows that immunosuppression may play a role in increasing the development of peri-implantitis. Along with need for further exploration regarding the pathophysiology of this relationship, additional observational and randomized controlled studies are necessary to validate the authors' findings. As implant restoration of edentulous areas is becoming the new standard of care, identification and understanding of associated risks factors are critical to ensure successful implant outcomes.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Variation in Immune-Related Gene Expression Provides Evidence of Local Adaptation in Porites astreoides (Lamarck, 1816) between Inshore and Offshore Meta-Populations Inhabiting the Lower Florida Reef Tract, USA

Coral communities of the Florida Reef Tract (FRT) have changed dramatically over the past 30 years. Coral cover throughout the FRT is disproportionately distributed; &gt;70% of total coral cover is found within the inshore patch reef zone (&lt;2 km from shore) compared to 30% found within the offshore bank reef zone (&gt;5 km from shore). Coral mortality from disease has been differentially observed between inshore and offshore reefs along the FRT. Therefore, differences between the response of inshore and offshore coral populations to bacterial challenge may contribute to differences in coral cover. We examined immune system activation in Porites astreoides (Lamarck, 1816), a species common in both inshore and offshore reef environments in the FRT. Colonies from a representative inshore and offshore site were reciprocally transplanted and the expression of three genes monitored biannually for two years (two summer and two winter periods). Variation in the expression of eukaryotic translation initiation factor 3, subunit H (eIF3H), an indicator of cellular stress in Porites astreoides, did not follow annual patterns of seawater temperatures (SWT) indicating the contribution of other stressors (e.g., irradiance). Greater expression of tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3), a signaling protein of the inflammatory response, was observed among corals transplanted to, or located within the offshore environment indicating that an increased immune response is associated with offshore coral more so than the inshore coral (p &lt; 0.001). Corals collected from the offshore site also upregulated the expression of adenylyl cyclase associated protein 2 (ACAP2), increases which are associated with decreasing innate immune system inflammatory responses, indicating a counteractive response to increased stimulation of the innate immune system. Activation of the innate immune system is a metabolically costly survival strategy. Among the two reefs studied, the offshore population had a smaller mean colony size and decreased colony abundance compared to the inshore site. This correlation suggests that tradeoffs may exist between the activation of the innate immune system and survival and growth. Consequently, immune system activation may contribute to coral community dynamics and declines along the FRT.

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm.

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

CD101 as an indicator molecule for pathological changes at the interface of host-microbiota interactions

Intestinal microbiota signal to local and distant tissues in the body. Thus, they also regulate biochemical, metabolic and immunological processes in the gut and in the pancreas. Vice versa, eating habits or the immune system of the host shape the intraluminal microbiota. Disruptions of these versatile host-microbiota interactions underlie the pathogenesis of complex immune-mediated disorders such as inflammatory bowel disease (IBD) or type 1 diabetes (T1D). Consequently, dysbiosis and increased intestinal permeability associated with both disorders change the biology of underlying tissues, as evidenced, for example, by an altered expression of surface markers such as CD101 on immune cells located at these dynamic host-microbiota interfaces.CD101, a heavily glycosylated member of the immunoglobulin superfamiliy, is predominantly detected on myeloid cells, intraepithelial lymphocytes (IELs) and regulatory T cells (Tregs) in the gut. The expression of CD101 on both myeloid cells and T lymphocytes protects from experimental enterocolitis and T1D. The improved outcome of both diseases is associated with an anti-inflammatory cytokine profile and a reduced expansion of T cells. However, distinct bacteria suppress the expression of CD101 on myeloid cells, similar as does inflammation on T cells. Thus, the reduced CD101 expression in T1D and IBD patients might be a consequence of an altered composition of the intestinal microbiota, enhanced bacterial translocation and a subsequent primining of local and systemic inflammatory immune responses.