Activating Natural Killer Cell Receptors, Selectins, and Inhibitory Siglecs Recognize Ebolavirus Glycoprotein
Expression of the extensively glycosylated Ebolavirus glycoprotein (EBOV-GP) induces physical alterations of surface molecules and plays a crucial role in viral pathogenicity. Here we investigate the interactions of EBOV-GP with host surface molecules using purified EBOV-GP, EBOV-GP-transfected cell lines, and EBOV-GP-pseudotyped lentiviral particles. Subsequently, we wanted to examine which receptors are involved in this recognition by binding studies to cells transfected with the EBOV-GP as well as to recombinant soluble EBOV-GP. As the viral components can also bind to inhibitory receptors of immune cells (e.g., Siglecs...
Source: Journal of Innate Immunity - August 23, 2021 Category: Allergy & Immunology Source Type: research
Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1 β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells
In this study, we investigated the role of pneumococcal-derived H2O2 in initiating epithelial cell death by analyzing the interplay between 2 key cell death pathways, namely, apoptosis and pyroptosis. We demonstrate that H2O2 primes as well as activates the NLRP3 inflammasome and thereby mediates IL-1 β production and release. Furthermore, we show that pneumococcal H2O2 causes cell death via the activation of both apoptotic as well as pyroptotic pathways which are mediated by the activation of caspase-3/7 and caspase-1, respectively. However, H2O2-mediated IL-1 β release itself occurs mainly via apoptosis.J Innate Immun ...
Source: Journal of Innate Immunity - August 6, 2021 Category: Allergy & Immunology Source Type: research
AhR Regulates Peptidoglycan-Induced Inflammatory Gene Expression in Human Keratinocytes
Bacterial peptidoglycan (PGN) stimulates toll-like receptor 2 (TLR2) on the surface of keratinocytes (KCs), triggering signaling pathways that promote an innate immune response. However, excessive TLR2 activation can lead to inappropriate inflammation, which contributes to skin conditions such as rosacea. To better treat these conditions, there is a need to understand the molecular mechanisms that regulate the cellular response to TLR2 activation in the skin. Aryl hydrocarbon receptor (AhR) is a transcription factor that modulates the immune response in KCs and is a promising therapeutic target for inflammatory skin diseas...
Source: Journal of Innate Immunity - August 5, 2021 Category: Allergy & Immunology Source Type: research
NF κB1 Dichotomously Regulates Pro-Inflammatory and Antiviral Responses in Asthma
Asthma exacerbations are commonly triggered by rhinovirus infections. Viruses can activate the NF κB pathway resulting in airway inflammation and increased Th2 cytokine expression. NFκB signaling is also involved in early activation of IFNβ, which is a central mediator of antiviral responses to rhinovirus infection. Using a mouse model, this study tests our hypothesis that NFκB signaling is involved in impaired IFNβ production at viral-induced asthma exacerbations. C57BL/6 wild-type and NFκB1−/− mice were challenged with house dust mite for 3 weeks and were subsequently stimulated with the rhinoviral mimic poly(I...
Source: Journal of Innate Immunity - July 28, 2021 Category: Allergy & Immunology Source Type: research
KDM6A Lysine Demethylase Directs Epigenetic Polarity of MDSCs during Murine Sepsis
In this study, we found by a genetic deletion that a specific PU.1-binding site is indispensable in controlling Hotairm1 transcription. We then identified H3K4me3 and H3K27me3 at the PU.1 site on the Hotairm1 promoter. Controlling an epigenetic switch of Hotairm1 transcription by PU.1 was histone KDM6A demethylase for H3K27me3 that derepressed its transcription with possible contributions from Ezh2 methyltransferase for H3K27me3. KDM6A knockdown in MDSCs increased H3K27me3, decreased H3K4me3, and inhibited Hotairm1 transcription activation by PU.1. These results enlighten clinical translation research of PU.1 epigenetic re...
Source: Journal of Innate Immunity - July 21, 2021 Category: Allergy & Immunology Source Type: research
Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress
In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - July 21, 2021 Category: Allergy & Immunology Source Type: research
Metabolic Regulation of Macrophage Activation
Macrophages, the central mediators of innate immune responses, being in the first-line of defense, they have to readily respond to pathogenic or tissue damage signals to initiate the inflammatory cascade. Such rapid responses require energy to support orchestrated production of pro-inflammatory mediators and activation of phagocytosis. Being a cell type that is present in diverse environments and conditions, macrophages have to adapt to different nutritional resources. Thus, macrophages have developed plasticity and are capable of utilizing energy at both normoxic and hypoxic conditions and in the presence of varying conce...
Source: Journal of Innate Immunity - July 9, 2021 Category: Allergy & Immunology Source Type: research
Intestinal Epithelial Cell-Derived CD83 Contributes to Regulatory T-Cell Generation and Inhibition of Food Allergy
Conclusion, IEC expresses CD83 that is low in sensitized mice. Concomitant administration of CD83 and specific antigens efficiently inhibits FA in a murine model via inducing Tregs in the intestine. The data suggest that CD83 has translation potential in the treatment of FA.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - June 28, 2021 Category: Allergy & Immunology Source Type: research
Time- and Stimulus-Dependent Characteristics of Innate Immune Cells in Organ-Cultured Human Corneal Tissue
Conclusions: Regarding different macrophage populations, untreated human corneas showed more M1 than M2 macrophages. With increasing organ culture time, these macrophages decreased. In terms of cell dynamics, adding interleukins to the organ culture medium influenced the phenotype of macrophages within the cornea as detected by FC. Modifying the immunomodulatory properties of human grafts appears a promising approach to further reduce the risk of graft rejection in patients. In this context, treatment with interleukins was more effective in upregulating M2 macrophages than in suppressing M1 macrophages in corneal tissue.J ...
Source: Journal of Innate Immunity - June 28, 2021 Category: Allergy & Immunology Source Type: research
Neuronal Dual Leucine Zipper Kinase Mediates Inflammatory and Nociceptive Responses in Cyclophosphamide-Induced Cystitis
Interstitial cystitis is associated with neurogenic inflammation and neuropathic bladder pain. Dual leucine zipper kinase (DLK) expressed in sensory neurons is implicated in neuropathic pain. We hypothesized that neuronal DLK is involved in the regulation of inflammation and nociceptive behavior in cystitis. Mice deficient in DLK in sensory neurons (cKO) were generated by crossing DLK floxed mice with mice expressing Cre recombinase under Advillin promoter. Cystitis was induced by cyclophosphamide (CYP) administration in mice. Nociceptive behavior, bladder inflammation, and pathology were assessed following cystitis induct...
Source: Journal of Innate Immunity - June 25, 2021 Category: Allergy & Immunology Source Type: research
Once Upon a Time
J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - June 9, 2021 Category: Allergy & Immunology Source Type: research
Exosomes Transport Anti-Human Immunodeficiency Virus Factors from Human Cervical Epithelial Cells to Macrophages
The female reproductive tract (FRT) is a major site of HIV sexual transmission. As the outermost layer of cells in the FRT, the human cervical epithelial cells (HCEs) have direct contact with HIV or infected cells. Our early work showed that supernatant (SN) from TLR3-activated HCEs contain the antiviral factors that could potently inhibit HIV replication in macrophages. However, it remains to be determined how HCEs transport the anti-HIV factors to macrophages. This follow-up study examined the role of exosomes in HCE-mediated anti-HIV activity. We found that TLR3 activation of HCEs resulted in the release of exosomes tha...
Source: Journal of Innate Immunity - June 3, 2021 Category: Allergy & Immunology Source Type: research
BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes
In conclusion, a proof of concept for inflammation attenuation of BAM15 through metabolic interference-induced anti-inflammation on macrophages and hepatocytes was demonstrated as a new strategy of anti-inflammation in sepsis.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - June 1, 2021 Category: Allergy & Immunology Source Type: research
TLR7 Ligation Inhibits TLR8 Responsiveness in IL-27-Primed Human THP-1 Monocytes and Macrophages
In this study, we focused on how the antiviral cytokine interleukin-27 (IL-27) regulates signal transduction downstream of Toll-like receptor 7 (TLR7) and TLR8 ligation, which recognize endosomal single-stranded RNA. Given that IL-27 alters bacterial-sensing TLR expression on myeloid cells and can inhibit replication of single-stranded RNA viruses, we investigated whether IL-27 affects expression and function of TLR7 and TLR8. Analysis of IL-27-treated THP-1 monocytic cells and THP-1-derived macrophages revealed changes in mRNA and protein expression of TLR7 and TLR8. Although treatment with IL-27 enhanced TLR7 expression,...
Source: Journal of Innate Immunity - May 31, 2021 Category: Allergy & Immunology Source Type: research
Hypoxia-Inducible Factor 1 Alpha Is Dispensable for Host Defense of Group B < b > < i > Streptococcus < /i > < /b > Colonization and Infection
Group BStreptococcus (GBS) is a leading cause of neonatal morbidity and mortality, and the primary source of exposure is the maternal vagina. Intrapartum antibiotic prophylaxis for GBS-positive mothers has reduced the incidence of GBS early-onset disease, however, potential long-lasting influence of an antibiotic-altered neonatal microbiota, and the frequent clinical sequelae in survivors of invasive GBS infection, compels alternative treatment options for GBS. Here, we examined the role of transcription factor hypoxia-inducible factor 1 alpha (HIF-1 α), widely recognized as a regulator of immune activation during infecti...
Source: Journal of Innate Immunity - May 21, 2021 Category: Allergy & Immunology Source Type: research
