Diacylglycerol kinases: at the hub of cell signalling

2007 ◽  
Vol 409 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Isabel Mérida ◽  
Antonia Ávila-Flores ◽  
Ernesto Merino
Keyword(s):  
Membrane Trafficking ◽  
Cell Signalling ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Intracellular Lipid ◽  
Cell Responses ◽  
Lipid Kinases ◽  
And Migration ◽  
Immune Dysfunctions

DGKs (diacylglycerol kinases) are members of a unique and conserved family of intracellular lipid kinases that phosphorylate DAG (diacylglycerol), catalysing its conversion into PA (phosphatidic acid). This reaction leads to attenuation of DAG levels in the cell membrane, regulating a host of intracellular signalling proteins that have evolved the ability to bind this lipid. The product of the DGK reaction, PA, is also linked to the regulation of diverse functions, including cell growth, membrane trafficking, differentiation and migration. In multicellular eukaryotes, DGKs provide a link between lipid metabolism and signalling. Genetic experiments in Caenorhabditis elegans, Drosophila melanogaster and mice have started to unveil the role of members of this protein family as modulators of receptor-dependent responses in processes such as synaptic transmission and photoreceptor transduction, as well as acquired and innate immune responses. Recent discoveries provide new insights into the complex mechanisms controlling DGK activation and their participation in receptor-regulated processes. After more than 50 years of intense research, the DGK pathway emerges as a key player in the regulation of cell responses, offering new possibilities of therapeutic intervention in human pathologies, including cancer, heart disease, diabetes, brain afflictions and immune dysfunctions.

scholarly journals High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

2021 ◽  
Vol 118 (40) ◽  
pp. e2109123118
Author(s):  
Magda Lourda ◽  
Majda Dzidic ◽  
Laura Hertwig ◽  
Helena Bergsten ◽  
Laura M. Palma Medina ◽  
...  
Keyword(s):  
Clinical Features ◽  
Innate Immune ◽  
High Dimensional ◽  
Innate Immune Responses ◽  
Altered Expression ◽  
Clinical Complications ◽  
Inflammatory State ◽  
Key Driver ◽  
And Migration

Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−infected patients is lacking. In this study, we used high-dimensional flow cytometry for granulocyte immunophenotyping in peripheral blood collected from COVID-19 patients during acute and convalescent phases. Severe COVID-19 was associated with increased levels of both mature and immature neutrophils, and decreased counts of eosinophils and basophils. Distinct immunotypes were evident in COVID-19 patients, with altered expression of several receptors involved in activation, adhesion, and migration of granulocytes (e.g., CD62L, CD11a/b, CD69, CD63, CXCR4). Paired sampling revealed recovery and phenotypic restoration of the granulocytic signature in the convalescent phase. The identified granulocyte immunotypes correlated with distinct sets of soluble inflammatory markers, supporting pathophysiologic relevance. Furthermore, clinical features, including multiorgan dysfunction and respiratory function, could be predicted using combined laboratory measurements and immunophenotyping. This study provides a comprehensive granulocyte characterization in COVID-19 and reveals specific immunotypes with potential predictive value for key clinical features associated with COVID-19.

scholarly journals Effects and Side Effects of Platelet Transfusion

2021 ◽  
Author(s):  
Fabrice Cognasse ◽  
Kathryn Hally ◽  
Sebastien Fauteux-Daniel ◽  
Marie-Ange Eyraud ◽  
Charles-Antoine Arthaud ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Responses ◽  
Platelet Transfusion ◽  
Biological Response ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Stress Injury ◽  
Processing And Storage ◽  
And Storage

AbstractAside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.

scholarly journals Regulation of dsDNA-induced innate immune responses by membrane trafficking

Autophagy ◽  
2010 ◽  
Vol 6 (3) ◽  
pp. 430-432 ◽  
Author(s):  
Tatsuya Saitoh ◽  
Naonobu Fujita ◽  
Tamotsu Yoshimori ◽  
Shizuo Akira
Keyword(s):  
Immune Responses ◽  
Membrane Trafficking ◽  
Innate Immune ◽  
Innate Immune Responses

Evolution of the diverse biological roles of inositols

2007 ◽  
Vol 74 ◽  
pp. 223-246 ◽  
Author(s):  
Robert H. Michell
Keyword(s):  
Membrane Trafficking ◽  
Cell Signalling ◽  
Compatible Solutes ◽  
Mirror Image ◽  
Membrane Phospholipids ◽  
Functional Diversification ◽  
Redox Reagent ◽  
Ca2 Channels ◽  
Mycobacterium Spp

Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology, with myo-inositol (Ins) in most of the starring roles; and Ins polyphosphates are amongst the most abundant organic phosphate constituents on Earth. Many Archaea make Ins and use it as a component of diphytanyl membrane phospholipids and the thermoprotective solute di-L-Ins-1,1′-phosphate. Few bacteria make Ins or use it, other than as a carbon source. Those that do include hyperthermophilic Thermotogales (which also employ di-l-Ins-1,1′-phosphate) and actinomycetes such as Mycobacterium spp. (which use mycothiol, an inositol-containing thiol, as an intracellular redox reagent and have characteristic phosphatidylinositol-linked surface oligosaccharides). Bacteria acquired their Ins3P synthases by lateral gene transfer from Archaea. Many eukaryotes, including stressed plants, insects, deep-sea animals and kidney tubule cells, adapt to environmental variation by making or accumulating diverse inositol derivatives as ‘compatible’ solutes. Eukaryotes use phosphatidylinositol derivatives for numerous roles in cell signalling and regulation and in protein anchoring at the cell surface. Remarkably, the diradylglycerol cores of archaeal and eukaryote/bacterial glycerophospholipids have mirror image configurations: sn-2,3 and sn-1,2 respectively. Multicellular animals and amoebozoans exhibit the greatest variety of functions for PtdIns derivatives, including the use of PtdIns(3,4,5)P3 as a signal. Evolutionarily, it seems likely that (i) early archaeons first made myo-inositol approx. 3500 Ma (million years) ago; (ii) archeons brought inositol derivatives into early eukaryotes (approx. 2000 Ma?); (iii) soon thereafter, eukaryotes established ubiquitous functions for phosphoinositides in membrane trafficking and Ins polyphosphate synthesis; and (iv) since approx. 1000 Ma, further waves of functional diversification in amoebozoans and metazoans have introduced Ins(1,4,5)P3 receptor Ca2+ channels and the messenger role of PtdIns(3,4,5)P3.

scholarly journals Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaoyao Xia ◽  
Yikun Li ◽  
Xiaoyan Wu ◽  
Qingzhuo Zhang ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Immune Responses ◽  
Epigenetic Regulation ◽  
Crucial Role ◽  
Liver Diseases ◽  
Iron Supplementation ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Innate Immune Responses

Iron fine-tunes innate immune responses, including macrophage inflammation. In this review, we summarize the current understanding about the iron in dictating macrophage polarization. Mechanistically, iron orchestrates macrophage polarization through several aspects, including cellular signaling, cellular metabolism, and epigenetic regulation. Therefore, iron modulates the development and progression of multiple macrophage-associated diseases, such as cancer, atherosclerosis, and liver diseases. Collectively, this review highlights the crucial role of iron for macrophage polarization, and indicates the potential application of iron supplementation as an adjuvant therapy in different inflammatory disorders relative to the balance of macrophage polarization.

scholarly journals TLR7 modulating B-cell immune responses in the spleen of C57BL/6 mice infected with Schistosoma japonicum

2021 ◽  
Vol 15 (11) ◽  
pp. e0009943
Author(s):  
Haixia Wei ◽  
Hongyan Xie ◽  
Jiale Qu ◽  
Anqi Xie ◽  
Shihao Xie ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Gene Knockout ◽  
Innate Immune ◽  
Wild Type ◽  
Cell Responses ◽  
Splenic Cells ◽  
And Function ◽  
Egg Antigen

B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S. japonicum for 5–6 weeks. The percentages and numbers of B cells increased in the infected mice (p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S. japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice (p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice (p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S. japonicum infected C57BL/6 mice.

scholarly journals The microbiota plays a critical role in the reactivity of lung immune components to innate ligands

2020 ◽  
Author(s):  
Quentin Marquant ◽  
Daphné Laubreton ◽  
Carole Drajac ◽  
Elliot Mathieu ◽  
Edwige Bouguyon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Immune Reactivity ◽  
Innate Immune Responses ◽  
Plain Language ◽  
Pulmonary Tissue ◽  
Germ Free ◽  
Syncytial Virus

AbstractThe microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota can modulate reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific pathogen-free (SPF) and germ-free (GF) mice. Using SPF and GF mice intranasally exposed to lipopolysaccharide (LPS), a component of Gram-negative bacteria, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.Plain Language summaryMicrobiota represents an important partner of immunologic system at the interface between immune cells and epithelium. It is well known, notably in the gut, that the microbiota contributes in shaping efficient and safe defenses. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. In this study, we postulate that endogenous microbiota could dampen an excessive reactivity of pulmonary tissue to external stimuli. Thus, we sought to study the innate immune reaction switched on by viral or bacterial ligands in respiratory tract cells coming from mice with or without microbiota (germ-free condition, GF). Altogether, our results show a higher inflammatory reaction in GF condition. This study represents a step forward to better establish the link between the microbiota and the reactivity of the lung tissue. Not only these data demonstrate that the microbiota educates the pulmonary innate immune system, but also contributes the emerging concept of using respiratory commensal bacteria as potential next-generation probiotics to prevent susceptibility to respiratory diseases.

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