< b > < i > Salmonella < /i > < /b > and Reactive Oxygen Species: A Love-Hate Relationship
Salmonella enterica represents an enterobacterial species including numerous serovars that cause infections at, or initiated at, the intestinal epithelium. Many serovars also act as facultative intracellular pathogens with a tropism for phagocytic cells. These bacteria not only survive in phagocytes but also undergo de facto replication therein. Phagocytes, through the activities of phagocyte NADPH-dependent oxidase and inducible nitric oxide synthase, are very proficient in converting molecular oxygen to reactive oxygen (ROS) and nitrogen species (RNS). These compounds represent highly efficient effectors of the innate im...
Source: Journal of Innate Immunity - April 3, 2019 Category: Allergy & Immunology Source Type: research
Erratum
J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - March 31, 2019 Category: Allergy & Immunology Source Type: research
< b > < i > Anopheles stephensi < /i > < /b > Dual Oxidase Silencing Activates the Thioester-Containing Protein 1 Pathway to Suppress < b > < i > Plasmodium < /i > < /b > Development
We characterized the dual oxidase (Duox) gene in the major Indian malaria vectorAnopheles stephensi, which regulates the generation of reactive oxygen species. The AsDuox gene encodes for a 1,475-amino-acid transmembrane protein that contains an N-terminal noncytoplasmic heme peroxidase domain, a calcium-binding domain, seven transmembrane domains, and a C-terminal cytoplasmic NADPH domain. Phylogenetic analyses revealed thatA. stephensi Duox protein is highly conserved and shares 97 –100% amino acid identity with other anopheline Duoxes. AsDuox is expressed in all the developmental stages ofA. stephensi and the pupal st...
Source: Journal of Innate Immunity - March 31, 2019 Category: Allergy & Immunology Source Type: research
Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type 2 Cytokines and Rhinovirus
This study was carried out to determine whether Tollip downregulates ST2 signaling via inhibition of IRAK1, but promotes soluble ST2 (sST2) production, thereby limiting excessive IL-8 production in human airway epithelial cells during RV infection in a type 2 cytokine milieu (e.g., IL-13 and IL-33 stimulation). Tollip- and IRAK1-deficient primary human tracheobronchial epithelial (HTBE) cells and Tollip knockout (KO) HTBE cells were generated using the shRNA knockdown and CRISPR/Cas9 approaches, respectively. Cells were stimulated with IL-13, IL-33, and/or RV16. sST2, activated IRAK1, and IL-8 were measured. A Tollip KO mo...
Source: Journal of Innate Immunity - March 31, 2019 Category: Allergy & Immunology Source Type: research
Mice Lacking Fatty Acid-Binding Protein 5 Are Resistant to < b > < i > Listeria monocytogenes < /i > < /b >
To investigate the role of fatty acid-binding protein 5 (FABP5) in infectious diseases, FABP5-deficient mice were challenged withListeria monocytogenes, a facultative intracellular bacterial pathogen. Interestingly, FABP5-deficient animals were able to clear the infection within 3 days whereas control wild-type (WT) animals showed comparatively higher bacterial burdens in the liver and spleen. Sections of infected tissues showed an increase in inflammatory foci in WT mice compared to FABP5-deficient mice. FABP5-deficient mice had lower circulating inflammatory cytokines and increased inducible nitric oxide synthase product...
Source: Journal of Innate Immunity - March 20, 2019 Category: Allergy & Immunology Source Type: research
Streptolysin O Induces the Ubiquitination and Degradation of Pro-IL-1 β
Group AStreptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1 β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1β. Ubiquitination was dep...
Source: Journal of Innate Immunity - March 20, 2019 Category: Allergy & Immunology Source Type: research
Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria
A successful colonization of different compartments of the human host requires multifactorial contacts between bacterial surface proteins and host factors. Extracellular matrix proteins and matricellular proteins such as thrombospondin-1 play a pivotal role as adhesive substrates to ensure a strong interaction with pathobionts like the Gram-positiveStreptococcus pneumoniae andStaphylococcus aureus. The human glycoprotein thrombospondin-1 is a component of the extracellular matrix and is highly abundant in the bloodstream during bacteremia. Human platelets secrete thrombospondin-1, which is then acquired by invading pathoge...
Source: Journal of Innate Immunity - March 7, 2019 Category: Allergy & Immunology Source Type: research
Bacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages
In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dep endent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tes...
Source: Journal of Innate Immunity - March 7, 2019 Category: Allergy & Immunology Source Type: research
Another Brick in the Wall
J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - February 26, 2019 Category: Allergy & Immunology Source Type: research
Coxsackievirus B Tailors the Unfolded Protein Response to Favour Viral Amplification in Pancreatic β Cells
Type 1 diabetes (T1D) is an autoimmune disease characterized by islet inflammation and progressive pancreatic β cell destruction. The disease is triggered by a combination of genetic and environmental factors, but the mechanisms leading to the triggering of early innate and late adaptive immunity and consequent progressive pancreatic β cell death remain unclear. The insulin-producing β cells are active s ecretory cells and are thus particularly sensitive to endoplasmic reticulum (ER) stress. ER stress plays an important role in the pathologic pathway leading to autoimmunity, islet inflammation, and β cell death. We sho...
Source: Journal of Innate Immunity - February 20, 2019 Category: Allergy & Immunology Source Type: research
Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition
The NLRP1 inflammasome attenuates inflammatory bowel disease (IBD) progression and colitis-associated tumorigenesis. A possible mechanism postulates that the lack of the NLRP1 inflammasome creates permissive niches in the gut for pathogenic bacteria to flourish, causing dysbiosis and increased IBD susceptibility. To evaluate this hypothesis, we characterized the gut microbiome of wild-type,Nlrp1b –/–, andAsc –/– mice under na ïve conditions by sequencing the V3 region of the 16s rRNA gene. For both genetically modified mouse lines, the microbiome composition reflected overrepresentation of bacteria associated with...
Source: Journal of Innate Immunity - February 14, 2019 Category: Allergy & Immunology Source Type: research
Group 2 Innate Lymphoid Cells in Human Respiratory Disorders
Recent studies using animal models have generated profound insight into the functions of various subsets of innate lymphoid cells (ILCs). The group 2 ILC subset (ILC2) has been implicated in tissue homeostasis, defense responses against parasites, tissue repair, and immunopathology associated with type-2 immunity. In addition, progress has also been made in translating these findings from animal studies into a context of human immunity. Importantly, recent observations strongly support a role for ILC2s in several diseases of the human respiratory system. However, many aspects of human ILC2 biology are still unclear, includ...
Source: Journal of Innate Immunity - February 6, 2019 Category: Allergy & Immunology Source Type: research
Innate Immune Mechanisms with a Focus on Small-Molecule Microbe-Host Cross Talk
J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - February 6, 2019 Category: Allergy & Immunology Source Type: research
CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor- α Production in a Macrophage Subset
In response to GM-CSF or M-CSF, macrophages (M Φ) can acquire pro- or anti-inflammatory properties, respectively. Given the importance of CD14 and Toll-like receptor (TLR) 4 in lipopolysaccharide (LPS)-induced signaling, we studied the effect of anti-CD14 antibody mediated CD14 blockade on LPS-induced cytokine production, signal transduction an d on the expression levels of CD14 and TLR4 in GM-MΦ and M-MΦ. We found M-MΦ to express higher levels of both surface antigens and to produce more interferon (IFN)-β and interleukin-10, but less tumor necrosis factor (TNF)-α than GM-MΦ. Blockage of CD14 at high LPS concentrat...
Source: Journal of Innate Immunity - January 17, 2019 Category: Allergy & Immunology Source Type: research
The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to < b > < i > Pseudomonas aeruginosa < /i > < /b >
In this report, we provide evidence that the conserved miR-183/96/182 cluster (miR-183/96/182) modulates Mϕ function in their production of reactive nitrogen (RNS) and oxygen species (ROS) and their inflammatory response toPseudomonas aeruginosa (PA) infection and/or lipopolysaccharide (LPS) treatment. We show that knockdown of miR-183/96/182 results in decreased production of multiple proinflammatory cytokines in response to PA or LPS treatment in M ϕ-like Raw264.7 cells. Consistently, peritoneal Mϕ from miR-183/96/182-knockout versus wild-type mice are less responsive to PA or LPS, although their basal levels of proin...
Source: Journal of Innate Immunity - January 13, 2019 Category: Allergy & Immunology Source Type: research
