Vitamin D, infections and immunity Ismailova, Aiten; White, John H.
Reviews in endocrine & metabolic disorders,
04/2022, Letnik:
23, Številka:
2
Journal Article
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Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the ...25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as
M. tuberculosis
. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.
Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune ...cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (
) and cathelicidin antimicrobial peptide (
) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led by Schultz (Nat Cell Biol 2: 695-702, ...2000) and Liedtke (Cell 103: 525-535, 2000). TRPV4 is now recognized as being a polymodal ionotropic receptor that is activated by a disparate array of stimuli, ranging from hypotonicity to heat and acidic pH. Importantly, this ion channel is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions, as does its widespread dissemination throughout the body and its capacity to interact with other proteins. Not surprisingly, therefore, it has emerged more recently that TRPV4 fulfills a great number of important physiological roles and that various disease states are attributable to the absence, or abnormal functioning, of this ion channel. Here, we review the known characteristics of this ion channel's structure, localization and function, including its activators, and examine its functional importance in health and disease.
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•The carbon market is growing.•Four carbon offset methodologies have been approved for wetland restoration.•Very few wetland restoration carbon offsets transected to ...date.•Simplification of existing methodologies may facilitate adoption of blue C offsets.
Coastal wetlands have been valued for a variety of ecosystem services including carbon sequestration and long term storage. The carbon sequestered and stored in coastal habitat including mangroves, salt marshes, and seagrass beds is termed as blue carbon. However, these systems are threatened mainly due to sea level rise, limited sediment supply, edge erosion, and anthropogenic influences. These habitats require restoration and conservation to continue providing ecosystem services. The incentive for emission reductions, referred to as carbon offsets, is well established for other ecosystems like forestry and agriculture. Some blue carbon offset methodologies or protocols have been certified by various voluntary carbon markets; however to date, a few wetland restoration carbon offset in the US has been transacted. Thus, the goal of this paper is to discuss the existing carbon market and carbon market methodologies applicable to coastal wetland restoration and conservation in the US. Currently, four wetland carbon offset methodologies have been approved in the carbon market. These methodologies are site and/or project-specific depending on the type of the wetlands, vulnerability to loss, and restoration need. The appropriate carbon stock and Green House Gas (GHG) emission assessment is the basis of determining carbon offsets. Simplification of the existing methodologies and development of new site and project-specific methodologies could potentially help to realize blue carbon offsets in practice. The slowly growing demand for carbon offsets in the carbon market could potentially be fulfilled from the blue carbon pool. While this carbon offset is in the early stages, this review may help the inclusion of carbon offset component in the coastal restoration and conservation projects in United States and potentially across the globe.
Abstract
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D ...receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D–deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
•Crohn’s disease (CD) arises from defective intestinal innate immunity.•Vitamin D has emerged as a major regulator of human innate immunity.•Emerging evidence suggests that vitamin D deficiency ...contributes to CD pathogenesis.•Vitamin D supplementation may be of benefit in clinical management of CD.
Vitamin D has emerged as a key regulator of innate immune responses to pathogen threat. The hormonal form of vitamin D signals through a nuclear receptor transcription factor and regulates gene transcription. Several papers have shown that vitamin D signaling is active both upstream and downstream of pattern recognition receptors, vanguards of innate immune responses. Crohn’s disease (CD) is a relapsing-recurring inflammatory bowel disease (IBD) that arises from dysregulated intestinal innate immunity. Indeed, genetic studies have identified several CD susceptibility markers linked to mechanisms of innate immune responses to infection. Interest in links between vitamin D deficiency and CD has grown substantially, particularly in the last five years. While a number of studies have consistently revealed an association between CD and vitamin D deficiency, recent experimental work has uncovered a compelling mechanistic basis for the contribution of vitamin D deficiency to the pathogenesis of the disease. Moreover, a number of intervention trials have provided generally solid evidence that robust vitamin D supplementation may be of therapeutic benefit to patients with CD. This review summarizes these laboratory and clinical findings.
Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an ...alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in place on a treadmill, thus “clamping” behavior and location, while we varied the treadmill speed to distinguish time elapsed from distance traveled. Hippocampal neurons were strongly influenced by time and distance, and less so by minor variations in location. Furthermore, the activity of different neurons reflected integration over time and distance to varying extents, with most neurons strongly influenced by both factors and some significantly influenced by only time or distance. Thus, hippocampal neuronal networks captured both the organization of time and distance in a situation where these dimensions dominated an ongoing experience.
•Hippocampal neurons fire in sequences during treadmill running•Hippocampal neuronal activity reflects location, time, and distance
Kraus et al. report that, during stationary treadmill running, hippocampal neuronal activity reflects integration of both time elapsed and distance traveled, in addition other salient features of experience.
A distinctive examination of post-9/11 films in relation to the Hollywood western . Explores how films such as Open Range, True Grit and Jane Got a Gun reinforce a conservative myth of America ...exceptionalism. Examines how these films reflect the United States’ post-9/11 uncertainties and highlight the importance of defending the homeland.
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