scholarly journals Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2

2019 ◽  
Vol 217 (3) ◽  
Author(s):  
José Luís Fachi ◽  
Cristiane Sécca ◽  
Patrícia Brito Rodrigues ◽  
Felipe Cézar Pinheiro de Mato ◽  
Blanda Di Luccia ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Immune Responses ◽  
Pseudomembranous Colitis ◽  
Short Chain Fatty Acid ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Responses ◽  
Predisposing Factor ◽  
Free Fatty Acid Receptor ◽  
The Impact

Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of acetate is remarkably beneficial in ameliorating disease. Mechanistically, we show that acetate enhances innate immune responses by acting on both neutrophils and ILC3s through its cognate receptor free fatty acid receptor 2 (FFAR2). In neutrophils, acetate-FFAR2 signaling accelerates their recruitment to the inflammatory sites, facilitates inflammasome activation, and promotes the release of IL-1β; in ILC3s, acetate-FFAR2 augments expression of the IL-1 receptor, which boosts IL-22 secretion in response to IL-1β. We conclude that microbiota-derived acetate promotes host innate responses to C. difficile through coordinate action on neutrophils and ILC3s.

scholarly journals Innate Immune Responses of Skin Mucosa in Common Carp (Cyprinus Carpio) Fed a Diet Supplemented with Galactooligosaccharides

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 438 ◽  
Author(s):  
Elzbieta Pietrzak ◽  
Jan Mazurkiewicz ◽  
Anna Slawinska
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Common Carp ◽  
Geometric Mean ◽  
Juvenile Fish ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Related Genes ◽  
The Impact ◽  
Skin Mucosa

Galactooligosaccharides (GOS) are well-known immunomodulatory prebiotics. We hypothesize that GOS supplemented in feed modulates innate immune responses in the skin-associated lymphoid tissue (SALT) of common carp. The aim of this study was to determine the impact of GOS on mRNA expression of the immune-related genes in skin mucosa. During the feeding trial, the juvenile fish (bodyweight 180 ± 5 g) were fed two types of diet for 50 days: control and supplemented with 2% GOS. At the end of the trial, a subset of fish was euthanized (n = 8). Skin mucosa was collected, and RNA was extracted. Gene expression analysis was performed with RT-qPCR to determine the mRNA abundance of the genes associated with innate immune responses in SALT, i.e., acute-phase protein (CRP), antimicrobial proteins (His2Av and GGGT5L), cytokines (IL1β, IL4, IL8, IL10, and IFNγ), lectin (CLEC4M), lyzosymes (LyzC and LyzG), mucin (M5ACL), peroxidase (MPO), proteases (CTSB and CTSD), and oxidoreductase (TXNL). The geometric mean of 40s s11 and ACTB was used to normalize the data. Relative quantification of the gene expression was calculated with ∆∆Ct. GOS upregulated INFγ (p ≤ 0.05) and LyzG (p ≤ 0.05), and downregulated CRP (p ≤ 0.01). We conclude that GOS modulates innate immune responses in the skin mucosa of common carp.

scholarly journals SARS-CoV-2-Indigenous Microbiota Nexus: Does Gut Microbiota Contribute to Inflammation and Disease Severity in COVID-19?

2021 ◽  
Vol 11 ◽  
Author(s):  
Indranil Chattopadhyay ◽  
Esaki M. Shankar
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Gut Microbiome ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Targeted Interventions ◽  
Promising Therapeutic Approach ◽  
Indigenous Microbiota ◽  
The Impact ◽  
Microbiome Profiling

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.

scholarly journals The Collision of Meta-Inflammation and SARS-CoV-2 Pandemic Infection

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Gabrielle P Huizinga ◽  
Benjamin H Singer ◽  
Kanakadurga Singer
Keyword(s):  
Immune Responses ◽  
Tissue Injury ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Immune Mediators ◽  
Diabetes Status ◽  
The Impact ◽  
Physiologic Role

Abstract The coronavirus disease 2019 (COVID-19) pandemic has forced us to consider the physiologic role of obesity in the response to infectious disease. There are significant disparities in morbidity and mortality by sex, weight, and diabetes status. Numerous endocrine changes might drive these varied responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including hormone and immune mediators, hyperglycemia, leukocyte responses, cytokine secretion, and tissue dysfunction. Studies of patients with severe COVID-19 disease have revealed the importance of innate immune responses in driving immunopathology and tissue injury. In this review we will describe the impact of the metabolically induced inflammation (meta-inflammation) that characterizes obesity on innate immunity. We consider that obesity-driven dysregulation of innate immune responses may drive organ injury in the development of severe COVID-19 and impair viral clearance.

Impact of Immunosuppressive Drugs on Adaptive and Innate Immune Responses to Aspergillus fumigatus Antigens.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2222-2222
Author(s):  
Holger Hebart ◽  
Andreas Mickan ◽  
Ziad Haddad ◽  
Juergen Loeffler ◽  
Jean-Paul Latge ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Invasive Aspergillosis ◽  
Immunosuppressive Agents ◽  
T Cell Responses ◽  
Innate Immune ◽  
Strong Impact ◽  
Innate Immune Responses ◽  
Cell Responses ◽  
The Impact

Abstract Appropriate activation of the innate and adaptive immune system is crucial for the successful control of invasive aspergillosis (IA). Acute and chronic graft-versus-host disease as well as corticosteroids were described as major risk factors for the development of IA. In this study, we assessed the impact of immunosuppressive agents (dexamethasone, rapamycin, Cyclosporin A, FK506) on the A. fumigatus induced activation of monocyte-derived immature dendritic cells (iDC) and A. fumigatus-specific T-cell responses in well established cell culture models. Immature DCs were found to be activated and to differentiate into mature DCs in response to A. fumigatus antigens. The upregulation of CD86 was inhibited by dexamethasone (D) in 3 out of 3 experiments, and of CD40 and CD80 in 2/3. CSA and FK506 had a variable impact on the upregulation of CD86, but not on CD40 and CD80, whereas the expression of co-stimulatory molecules was found unchanged upon incubation with rapamycin. Autologous DCs were found to restore A. fumigatus-specific T-cell responses. T-cell proliferation to A. fumigatus hyphae and a cellular extract of the culture filtrate were found to be strongly inhibited by rapamycin and dexamethasone (n=3), whereas the effect of CSA and FK506 (n=3) at the concentrations analysed was variable. The release of IFN-g in culture supernatants upon stimulation with A. fumigatus antigens was strongly reduced in the presence of rapamycin (n=3), whereas the release of IL-4 was found to be increased in the majority of experiments (n=3). Comparable results were observed upon stimulation with tetanus toxoid and a CMV lysate (n=3). These data indicate, that A. fumigatus-spec. T-cell responses may be directed towards a TH2 phenotype in the presence of immunosuppressive agents. In summary, immunosuppressive agents were found to exert differential effects on adaptive and innate immune responses directed against A. fumigatus. Whereas dexamethasone was found to modulate the expression of co-stimulatory molecules on A. fumigatus activated iDCs and to suppress A. fumigatus-specific lymphoproliferation, rapamycin exerted only minor effects on DC-activation but had a strong impact on A. fumigatus-induced T-cell responses. These results may help to tailor immunosuppressive regimens in patients at high risk for invasive aspergillosis.

scholarly journals Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection

2020 ◽  
Vol 6 (38) ◽  
pp. eabb4565
Author(s):  
Bruno Hernáez ◽  
Graciela Alonso ◽  
Iliana Georgana ◽  
Misbah El-Jesr ◽  
Rocío Martín ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Therapeutic Strategy ◽  
Innate Immune ◽  
Protective Mechanism ◽  
Innate Immune Responses ◽  
Dna Sensing ◽  
Nuclease Domain ◽  
The Impact

Cells contain numerous immune sensors to detect virus infection. The cyclic GMP-AMP (cGAMP) synthase (cGAS) recognizes cytosolic DNA and activates innate immune responses via stimulator of interferon genes (STING), but the impact of DNA sensing pathways on host protective responses has not been fully defined. We demonstrate that cGAS/STING activation is required to resist lethal poxvirus infection. We identified viral Schlafen (vSlfn) as the main STING inhibitor, and ectromelia virus was severely attenuated in the absence of vSlfn. Both vSlfn-mediated virulence and STING inhibitory activity were mapped to the recently discovered poxin cGAMP nuclease domain. Animals were protected from subcutaneous, respiratory, and intravenous infection in the absence of vSlfn, and interferon was the main antiviral protective mechanism controlled by the DNA sensing pathway. Our findings support the idea that manipulation of DNA sensing is an efficient therapeutic strategy in diseases triggered by viral infection or tissue damage–mediated release of self-DNA.

scholarly journals Mitochondria: powering the innate immune response to Mycobacterium tuberculosis infection

2021 ◽  
Author(s):  
Kristin L. Patrick ◽  
Robert O. Watson
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Bacterial Pathogen ◽  
Tuberculosis Patient ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Type I ◽  
Innate Immune Responses ◽  
Mycobacterium Tuberculosis Infection

Within the last decade, we have learned that damaged mitochondria activate many of the same innate immune pathways that evolved to sense and respond to intracellular pathogens. These shared responses include cytosolic nucleic acid sensing and type I interferon (IFN) expression, inflammasome activation that leads to pyroptosis, and selective autophagy (called mitophagy when mitochondria are the cargo). Because mitochondria were once bacteria, parallels between how cells respond to mitochondrial and bacterial ligands are not altogether surprising. However, the potential for crosstalk or synergy between bacteria- and mitochondria-driven innate immune responses during infection remains poorly understood. This interplay is particularly striking—and intriguing—in the context of infection with the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). Multiple studies point to a role for Mtb infection and/or specific Mtb virulence factors in disrupting the mitochondrial network in macrophages leading to metabolic changes and triggering potent innate immune responses. Research from our labs and others argues that mutations in mitochondrial genes can exacerbate mycobacterial disease severity by hyper-activating innate responses or activating them at the wrong time. Indeed, growing evidence supports a model whereby different mitochondrial defects or mutations alter Mtb infection outcomes in distinct ways. By synthesizing the current literature in this minireview, we hope to gain insight into the molecular mechanisms driving, and consequences of, mitochondrial-dependent immune polarization so that we might better predict tuberculosis patient outcomes and develop host-directed therapeutics designed to correct these imbalances.

Mitochondrial DNA in innate immune responses against infectious diseases

2020 ◽  
Vol 48 (6) ◽  
pp. 2823-2838
Author(s):  
Palamou Das ◽  
Oishee Chakrabarti
Keyword(s):  
Immune Response ◽  
Mitochondrial Dna ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Mitochondrial Dynamics ◽  
Innate Immune ◽  
Activation Mechanism ◽  
Inflammasome Activation ◽  
Innate Immune Responses

Mitochondrial DNA (mtDNA) can initiate an innate immune response when mislocalized in a compartment other than the mitochondrial matrix. mtDNA plays significant roles in regulating mitochondrial dynamics as well as mitochondrial unfolded protein response (UPR). The mislocalized extra-mtDNA can elicit innate immune response via cGAS–STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway, inducing the expression of the interferon-stimulated genes (ISGs). Also, cytosolic damaged mtDNA is cleared up by various pathways which are responsible for participating in the activation of inflammatory responses. Four pathways of extra-mitochondrial mtDNA clearance are highlighted in this review — the inflammasome activation mechanism, neutrophil extracellular traps formation, recognition by Toll-like receptor 9 and transfer of mtDNA between cells packaged into extracellular vesicles. Anomalies in these pathways are associated with various diseases. We posit our review in the present pandemic situation and discuss how mtDNA elicits innate immune responses against different viruses and bacteria. This review gives a comprehensive picture of the role of extra-mitochondrial mtDNA in infectious diseases and speculates that research towards its understanding would help establish its therapeutic potential.

scholarly journals In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut

2007 ◽  
Vol 104 (18) ◽  
pp. 7622-7627 ◽  
Author(s):  
John F. Rawls ◽  
Michael A. Mahowald ◽  
Andrew L. Goodman ◽  
Chad M. Trent ◽  
Jeffrey I. Gordon
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Microbial Interactions ◽  
Microbial Consortia ◽  
Innate Immune Responses ◽  
Germ Free ◽  
Evolutionarily Conserved ◽  
Bacterial Genes ◽  
The Impact

Complex microbial communities reside within the intestines of humans and other vertebrates. Remarkably little is known about how these microbial consortia are established in various locations within the gut, how members of these consortia behave within their dynamic ecosystems, or what microbial factors mediate mutually beneficial host–microbial interactions. Using a gnotobiotic zebrafish–Pseudomonas aeruginosa model, we show that the transparency of this vertebrate species, coupled with methods for raising these animals under germ-free conditions can be used to monitor microbial movement and localization within the intestine in vivo and in real time. Germ-free zebrafish colonized with isogenic P. aeruginosa strains containing deletions of genes related to motility and pathogenesis revealed that loss of flagellar function results in attenuation of evolutionarily conserved host innate immune responses but not conserved nutrient responses. These results demonstrate the utility of gnotobiotic zebrafish in defining the behavior and localization of bacteria within the living vertebrate gut, identifying bacterial genes that affect these processes, and assessing the impact of these genes on host–microbial interactions.

scholarly journals CD1d-Associated Expression of NF-κB and Cardiac Dysfunction in Diabetic and Obese Mice

2013 ◽  
Vol 26 (1) ◽  
pp. 59-73 ◽  
Author(s):  
R. Madonna ◽  
H. Wu ◽  
H. Shelat ◽  
Y-J. Geng
Keyword(s):  
Immune Responses ◽  
Knockout Mice ◽  
Cardiac Dysfunction ◽  
Splenic Tissue ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Innate Immune Responses ◽  
Obesity And Diabetes ◽  
Tnf Α ◽  
The Impact

In patients with obesity and diabetes mellitus, abnormal production of inflammatory factors may result in cardiovascular dysfunction. In the current study, we tested the impact of CD1d-mediated innate immune responses on the expression and activation of NFκB in the hearts of adipose diabetic ( db/db) mice. Splenocytes from adult db/db and CD1d-knockout mice of both genders and their wild-type, C57BL/6 and Balb/C counterparts were examined for tumor necrosis factor (TNF)-α and TNF-α receptor type 1. The percentage of natural killer T (NKT) cells in CD3+ T cells was compared with that in nondiabetic control mice. Despite the absence of inflammatory infiltrates, the hearts of db/db mice showed alterations in TNF-α receptor-1 and NFκB activity, including increased expression of both the NFκB p52 and p65 subunits. In the hearts of CD1d-knockout mice, p52 expression was reduced, while p65 expression remained largely unchanged. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was significantly decreased in db/db mice after they swam for 30 minutes. These results provide evidence for CD1d-mediated NFκB activation and diastolic dysfunction in the hearts of db/db mice. Therefore, CD1d-associated abnormalities of innate immune responses and TNF-α production in splenic tissue may contribute to NFκB activation and cardiac dysfunction in type 2 diabetes.

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