Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery
Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL−/− ...
Source: Journal of Innate Immunity - June 7, 2022 Category: Allergy & Immunology Source Type: research
Regulation of TLR10 Expression and Its Role in Chemotaxis of Human Neutrophils
Toll-like receptors are innate immune receptors that play a critical role in pathogen-associated molecular pattern recognition. TLR10 was recently identified and very limited data are available on its expression, mechanisms that regulate its expression, and its role in primary immune cells. To study the expression pattern of TLR10 in primary immune cells, we examined TLR10 protein expression in naive andEscherichia coli lipopolysaccharide (LPS)-activated human neutrophils. Human neutrophils challenged with LPS showed a decrease in total and surface TLR10 expression at 90 min. TLR10 in LPS-activated neutrophils colocalized ...
Source: Journal of Innate Immunity - May 25, 2022 Category: Allergy & Immunology Source Type: research
miR-142-5p Encapsulated by Serum-Derived Extracellular Vesicles Protects against Acute Lung Injury in Septic Rats following Remote Ischemic Preconditioning via the PTEN/PI3K/Akt Axis
This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF- α and IL-6 l...
Source: Journal of Innate Immunity - May 19, 2022 Category: Allergy & Immunology Source Type: research
Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex
Damage and disease of nerves activates the complement system. We demonstrated that activation of the terminal pathway of the complement system leads to the formation of the membrane attack complex (MAC) and delays regeneration in the peripheral nervous system. Animals deficient in the complement component C6 showed improved recovery after neuronal trauma. Thus, inhibitors of the MAC might be of therapeutic use in neurological disease. Here, we describe the development, structure, mode of action, and properties of a novel therapeutic monoclonal antibody, CP010, against C6 that prevents formation of the MAC in vivo. The mono...
Source: Journal of Innate Immunity - May 12, 2022 Category: Allergy & Immunology Source Type: research
IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19
We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1 α...
Source: Journal of Innate Immunity - May 11, 2022 Category: Allergy & Immunology Source Type: research
Bruton ’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against < b > < i > Klebsiella pneumoniae < /i > < /b >
In this study, we determined the contribution of Btk in B cells and neutrophils to host defense against the extracellular bacterial pathogenKlebsiella pneumoniae, a common cause of pulmonary infections and sepsis.Btk−/− mice were highly susceptible toKlebsiella infection, which was not reversed by Btk re-expression in B cells and restoration of natural antibody levels. Neutrophil-specific Btk deficiency impaired host defense againstKlebsiella to a similar extent as complete Btk deficiency. Neutrophil-specific Btk deficiency abolished extracellular reactive oxygen species production in response toKlebsiella. These data ...
Source: Journal of Innate Immunity - May 10, 2022 Category: Allergy & Immunology Source Type: research
Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions
The primary cause of morbidity and mortality from infection with respiratory syncytial virus (RSV) is the excessive innate immune response(s) (IIR) in which reactive oxygen species (ROS) play key role(s). However, the mechanisms for these processes are not fully understood. We hypothesized that expressions of IIR genes are controlled by the ROS-generated epigenetic-like mark 7,8-dihydro-8-oxo(d)guanine (8-oxo(d)Gua) and 8-oxoguanine DNA glycosylase1 (OGG1). Here, we report that ROS not only generates intrahelical 8-oxo(d)Gua, but also enzymatically disables OGG1 in RSV-infected human airway epithelial cells and mouse lungs...
Source: Journal of Innate Immunity - May 5, 2022 Category: Allergy & Immunology Source Type: research
HMGB1-Like Dorsal Switch Protein 1 Triggers a Damage Signal in Mosquito Gut to Activate Dual Oxidase via Eicosanoids
This study proposed a hypothesis that a damage signal might be specifically induced by pathogens in the gut. The Asian tiger mosquito,Aedes albopictus, encodes dorsal switch protein 1 (Aa-DSP1) as a putative damage-associated molecular pattern (DAMP). Aa-DSP1 was localized in the nucleus of the midgut epithelium in na ïve larvae. Upon infection by a pathogenic bacterium,Serratia marcescens, Aa-DSP1 was released to hemocoel and activated phospholipase A2 (PLA2). The activated PLA2 increased the level of prostaglandin E2 (PGE2) in the gut and subsequently increased Ca2+ signal to produce reactive oxygen species (ROS) via du...
Source: Journal of Innate Immunity - May 5, 2022 Category: Allergy & Immunology Source Type: research
High Infiltration of CD68 < sup > + < /sup > /CD163 < sup > − < /sup > Macrophages Is an Adverse Prognostic Factor after Neoadjuvant Chemotherapy in Esophageal and Gastric Adenocarcinoma
In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - May 3, 2022 Category: Allergy & Immunology Source Type: research
< b > < i > Staphylococcus aureus < /i > < /b > Activates the Aryl Hydrocarbon Receptor in Human Keratinocytes
Staphylococcus aureus is an important pathogen causing various infections, including – as most frequently isolated bacterium – cutaneous infections. Keratinocytes as the first barrier cells of the skin respond toS. aureus by the release of defense molecules such as cytokines and antimicrobial peptides. Although several pattern recognition receptors expressed in keratinocytes such as Toll-like and NOD-like receptors have been reported to detect the presence ofS. aureus, the mechanisms underlying the interplay betweenS. aureus and keratinocytes are still emerging. Here, we report thatS. aureus induced gene expression of ...
Source: Journal of Innate Immunity - May 2, 2022 Category: Allergy & Immunology Source Type: research
SP1 Promotes HDAC4 Expression and Inhibits HMGB1 Expression to Reduce Intestinal Barrier Dysfunction, Oxidative Stress, and Inflammatory Response after Sepsis
As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobili...
Source: Journal of Innate Immunity - April 22, 2022 Category: Allergy & Immunology Source Type: research
GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus
Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor- β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) o r deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymph...
Source: Journal of Innate Immunity - April 20, 2022 Category: Allergy & Immunology Source Type: research
Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury
Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasalEscherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid med...
Source: Journal of Innate Immunity - April 1, 2022 Category: Allergy & Immunology Source Type: research
The Capsule of < b > < i > Acinetobacter baumannii < /i > < /b > Protects against the Innate Immune Response
This study underscores the role of phase variation in the modulation of host immune responses and indicates that the capsule ofA. baumannii plays an important role in protection against host cell killing and evasion from activation of the innate immune response.J Innate Immun (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - March 23, 2022 Category: Allergy & Immunology Source Type: research
The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases
Citrullination of proteins is crucial for the formation of neutrophil extracellular traps (NETs) – strands of nuclear DNA expulsed in the extracellular environment along with antimicrobial proteins in order to halt the spread of pathogens. Paradoxically, NETs may be immunogenic and contribute to inflammation. It is known that for the externalization of DNA, a group of enzymes called peptidyl arginine deiminases (PADs) is required. Current research often looks at citrullination, NET formation, PAD overexpression, and extracellular DNA (ecDNA) accumulation in chronic diseases as separate events. In contrast, we propose tha...
Source: Journal of Innate Immunity - March 9, 2022 Category: Allergy & Immunology Source Type: research
