Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study
Conclusion: These results provide evidence for the involvement of innate immune pathways and myeloid cells during human anaphylaxis, validating previous microarray findings. ElevatedS100A8,S100A9,TLR4, andTREM1 expression, and increased S100A9 and soluble TREM1 protein concentrations strongly suggest that neutrophils are activated during acute anaphylaxis.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - September 7, 2018 Category: Allergy & Immunology Source Type: research
Chemokine Subversion by Human Herpesviruses
Viruses use diverse molecular mechanisms to exploit and evade the immune response. Herpesviruses, in particular, encode functional chemokine and chemokine receptor homologs pirated from the host, as well as secreted chemokine-binding proteins with unique structures. Multiple functions have been described for herpesvirus chemokine components, including attraction of target cells, blockade of leukocyte migration, and modulation of gene expression and cell entry by the virus. Here we review current concepts about how human herpesvirus chemokines, chemokine receptors, and chemokine-binding proteins may be used to shape a provi...
Source: Journal of Innate Immunity - September 2, 2018 Category: Allergy & Immunology Source Type: research
Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications
Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the deve...
Source: Journal of Innate Immunity - August 27, 2018 Category: Allergy & Immunology Source Type: research
Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application
Highly antibiotic resistant, microbial communities, referred to as biofilms, cause various life-threatening infections in humans. At least two-thirds of all clinical infections are biofilm associated, and antibiotic therapy regularly fails to cure patients. Anti-biofilm peptides represent a promising approach to treat these infections by targeting biofilm-specific characteristics such as highly conserved regulatory mechanisms. They are being considered for clinical application and we discuss here key factors in discovery, design, and application, particularly the implementation of host-mimicking conditions, that are requir...
Source: Journal of Innate Immunity - August 22, 2018 Category: Allergy & Immunology Source Type: research
Aryl Hydrocarbon Receptor Modulates the Expression of TNF- α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways
In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF- α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF- α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repre...
Source: Journal of Innate Immunity - July 27, 2018 Category: Allergy & Immunology Source Type: research
Hoodwinking the Big-Eater to Prosper: The < b > < i > Salmonella < /i > < /b > -Macrophage Paradigm
Salmonella is a major cause of morbidity and mortality in the developing and underdeveloped nations. Being a foodborne disease,Salmonella infection is primarily contracted through the ingestion of contaminated food or water, or due to close contact with infected/carrier individuals. It is an intracellular pathogen, which can survive and replicate in various cells including macrophages, dendritic cells, epithelial cells, and other white blood cells. OnceSalmonella crosses the intestinal barrier, it disseminates to various systemic sites by circulation via immune cells. One of the major cell types which are involved inSalmon...
Source: Journal of Innate Immunity - July 24, 2018 Category: Allergy & Immunology Source Type: research
Human Cervical Epithelial Cells Release Antiviral Factors and Inhibit HIV Replication in Macrophages
The female reproductive tract is a major site of HIV sexual transmission. We here examined whether human cervical epithelial cells (HCEs) can be immunologically activated and produce antiviral factors against HIV. We demonstrated that HCEs (End1/E6E7 cells) possess the functional toll-like receptor (TLR)3 signaling system, which could be activated by Poly I:C and induce multiple cellular HIV restriction factors. The treatment of primary human macrophages with supernatant (SN) from TLR3-activated End1/E6E7 cell cultures resulted in HIV inhibition. This SN-mediated HIV inhibition was mainly through the induction of interfe...
Source: Journal of Innate Immunity - July 20, 2018 Category: Allergy & Immunology Source Type: research
The Anaphylatoxin C3a Receptor Expression on Human M2 Macrophages Is Down-Regulated by Stimulating the Histamine H4 Receptor and the IL-4 Receptor
The anaphylatoxin C3a triggers inflammation by binding to its specific G-protein-coupled C3a receptor (C3aR). Since the number of C3aR, which is expressed on the cell surface, affects the response to C3a, we investigated the expression levels of C3aR on human M2 macrophages in allergic situations where high levels of the Th2 cytokine IL-4 and histamine are present in a local microenvironment. The histamine H1 receptor (H1R), H2R and the H4R mRNA expressions were induced or up-regulated during the differentiation process of M2 macrophages. The presence of histamine or agonists targeting the H1R, H2R and, in particular, the ...
Source: Journal of Innate Immunity - July 20, 2018 Category: Allergy & Immunology Source Type: research
Potential Role of Gr-1 < sup > + < /sup > CD8 < sup > + < /sup > T Lymphocytes as a Source of Interferon- γ and M1/M2 Polarization during the Acute Phase of Murine < b > < i > Legionella pneumophila < /i > < /b > Pneumonia
In this study, we analyzed interferon (IFN)- γ-producing cells and M1/M2 macrophage polarization inLegionella pneumophila pneumonia following anti-Gr-1 antibody treatment. Anti-Gr-1 treatment induced an M1-to-M2 shift of macrophage subtypes in the lungs and weakly in the peripheral blood, which was associated with increased mortality in legionella-infected mice. CD8+ T lymphocytes and natural killer cells were the dominant sources of IFN- γ in the acute phase, and anti-Gr-1 treatment reduced the number of IFN-γ-producing CD8+ T lymphocytes. In the CD3-gated population, most Gr-1-positive cells were CD8+ T lymphocytes in...
Source: Journal of Innate Immunity - July 18, 2018 Category: Allergy & Immunology Source Type: research
PLA1A Participates in the Antiviral Innate Immune Response by Facilitating the Recruitment of TANK-Binding Kinase 1 to Mitochondria
In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate immune signaling induced by RNA viruses, while PLA1A overexpression enhanced the signaling. PLA1A functioned at the TBK1 level of the signaling pathway, as PLA1A silencing blocked TBK1, but not interferon regulatory factor 3 (IRF3) induced interferon- β (IFN-β) promoter activity. The phosphorylation and kinase activity of TBK1 was reduced in PLA1A knockdown cells. Mechanistically, PLA1A was required in TBK1-mitochondrial antiviral signaling ...
Source: Journal of Innate Immunity - July 17, 2018 Category: Allergy & Immunology Source Type: research
Characterization of Pattern Recognition Receptor Expression and Functionality in Liver Primary Cells and Derived Cell Lines
Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still missing. In order to comparatively characterize these pathways, we purified primary human hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells (LSEC), and Kupffer cells (KC) from human liver resections. We assessed mRNA and protein expression level of the major innate immune sensors, as well ...
Source: Journal of Innate Immunity - July 5, 2018 Category: Allergy & Immunology Source Type: research
Unique < b > < i > Francisella < /i > < /b > Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid
VirulentFrancisella tularensis subsp.tularensis (Ftt) is a dynamic, intracellular, bacterial pathogen. Its ability to evade and rapidly suppress host inflammatory responses is considered a key element for its profound virulence. We previously established that Ftt lipids play a role in inhibiting inflammation, but we did not determine the lipid species mediating this process. Here, we show that a unique, abundant, phosphatidylethanolamine (PE), present inFrancisella, contributes to driving the suppression of inflammatory responses in human and mouse cells. Acyl chain lengths of this PE, C24: 0 and C10: 0, were key to the su...
Source: Journal of Innate Immunity - July 3, 2018 Category: Allergy & Immunology Source Type: research
Myeloid-Derived Suppressor Cells in Infection: A General Overview
After initial infection, the immune response that serves to restrict the invading pathogen needs to be tightly calibrated in order to avoid collateral immunopathological damage. This calibration is performed by specialized suppressor mechanisms, which are capable of dampening overwhelming or unremitting inflammation in order to prevent tissue damage. Myeloid-derived suppressor cells (MDSC) are emerging as key players in counter-balancing inflammatory responses and pathogenesis during infection. However, some pathogens are able to exploit the suppressive activities of MDSC to favor pathogen persistence and chronic infection...
Source: Journal of Innate Immunity - June 26, 2018 Category: Allergy & Immunology Source Type: research
Spleen Tyrosine Kinase as a Target Therapy for < b > < i > Pseudomonas aeruginosa < /i > < /b > Infection
Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase which associates directly with extracellular receptors, and is critically involved in signal transduction pathways in a variety of cell types for the regulation of cellular responses. SYK is expressed ubiquitously in immune and nonimmune cells, and has a much wider biological role than previously recognized. Several studies have highlighted SYK as a key player in the pathogenesis of a multitude of diseases.Pseudomonas aeruginosa is an opportunistic gram-negative pathogen, which is responsible for systemic infections in immunocompromised individuals, accounting f...
Source: Journal of Innate Immunity - June 20, 2018 Category: Allergy & Immunology Source Type: research
Short-Form Bomanins Mediate Humoral Immunity in < b > < i > Drosophila < /i > < /b >
The Bomanins (Boms) are a family of a dozen secreted peptides that mediate the innate immune response governed by theDrosophila Toll receptor. We recently showed that deleting a cluster of 10Bom genes blocks Toll-mediated defenses against a range of fungi and gram-positive bacteria. Here, we characterize the activity of individual Bom family members. We provide evidence that the Boms overlap in function and that a singleBom gene encoding a mature peptide of just 16 amino acids can act largely or entirely independent of other family members to provide phenotypic rescue in vivo. We further demonstrate that theBoms function i...
Source: Journal of Innate Immunity - June 19, 2018 Category: Allergy & Immunology Source Type: research
