scholarly journals Differential Modulation of 25-hydroxycholecalciferol on Innate Immunity of Broiler Breeder Hens

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1742
Author(s):  
Pao-Chia Chou ◽  
Pei-Chi Lin ◽  
Shu-Wei Wu ◽  
Chien-Kai Wang ◽  
Thau-Kiong Chung ◽  
...  
Keyword(s):  
Feed Intake ◽  
Respiratory Burst ◽  
Immune Cell ◽  
Growth Period ◽  
Dependent Manner ◽  
Immune Functions ◽  
Bacterial Killing ◽  
Cell Functions ◽  
Breeder Hens ◽  
25 Hydroxycholecalciferol

Past immunological studies in broilers focused on juveniles within the rapid pre-slaughter growth period and may not reflect adult immune responses, particularly in breeders managed with chronic feed restriction (R). The study aimed to assess innate immune cell functions in respect to R vs. ad libitum (Ad) feed intake in breeder hens with and without dietary 25-hydroxycholecalciferol (25-OH-D3) supplementation. Ad-feed intake consistently suppressed IL-1β secretion, respiratory burst, and cell livability in peripheral heterophils and/or monocytes along the feeding trial from the age of 51 to 68 weeks. Supplemental 25-OH-D3 repressed IL-1β secretion and respiratory burst of both cells mostly in R-hens, but promoted monocyte phagocytosis, chemotaxis, and bacterial killing activity in Ad-hens in accompany with relieved hyperglycemia, hyperlipidemia, and systemic inflammation. Overnight cultures with leukocytes from R-hens confirmed the differential effects of 25-OH-D3 to rescue immune functions altered by glucose and/or palmitic acid exposure. Studies with specific inhibitors further manifested the operative mechanisms via glucolipotoxicity in a cell type- and function-dependent manner. The results concluded no predominant changes between R- vs. Ad-feed intake on leukocyte defense against pathogens despite some differential differences, but supplemental 25-OH-D3 exerts more pronounced effects in Ad-hens.

scholarly journals Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7

2020 ◽  
Vol 133 (14) ◽  
pp. jcs244400 ◽  
Author(s):  
Madhavi Vijayan ◽  
Cheuk-Lun Lee ◽  
Vera H. H. Wong ◽  
Xia Wang ◽  
Kungfeng Bai ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Immune Cell ◽  
Fetal Loss ◽  
Cell Types ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Placental Development ◽  
Cell Functions ◽  
Surface Marker Expression ◽  
Glycodelin A

ABSTRACTDecidual macrophages constitute 20–30% of the total leukocytes in the uterus of pregnant women, regulating the maternal immune tolerance and placenta development. Abnormal number or activities of decidual macrophages (dMs) are associated with fetal loss and pregnancy complications, such as preeclampsia. Monocytes differentiate into dMs in a decidua-specific microenvironment. Despite their important roles in pregnancy, the exact factors that regulate the differentiation into dMs remain unclear. Glycodelin-A (PAEP, hereafter referred to as GdA) is a glycoprotein that is abundantly present in the decidua, and plays an important role in fetomaternal defense and placental development. It modulates the differentiation and activity of several immune cell types residing in the decidua. In this study, we demonstrated that GdA induces the differentiation of human monocytes into dM-like phenotypes in terms of transcriptome, cell surface marker expression, secretome, and regulation of trophoblast and endothelial cell functions. We found that Sialic acid-binding Ig-like lectin 7 (Siglec-7) mediates the binding and biological actions of GdA in a sialic acid-dependent manner. We, therefore, suggest that GdA, induces the polarization of monocytes into dMs to regulate fetomaternal tolerance and placental development.

scholarly journals The Alzheimer’s disease-associated protective Plcγ2-P522R variant promotes immune functions

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Mari Takalo ◽  
Rebekka Wittrahm ◽  
Benedikt Wefers ◽  
Samira Parhizkar ◽  
Kimmo Jokivarsi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cell ◽  
Therapeutic Option ◽  
Immune Functions ◽  
Disease Etiology ◽  
Cell Functions ◽  
Bv2 Microglia ◽  
Brain Mrna ◽  
Protective Variant

Abstract Background Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer’s disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in the PLCG2 gene (rs72824905, p.P522R) expressed in myeloid lineage cells was recently identified and shown to reduce the risk for AD. Methods To assess the role of the protective variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing. Results Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme. This was associated with improved survival and increased acute inflammatory response of the KI macrophages. Enhanced phagocytosis was observed in mouse BV2 microglia-like cells overexpressing human PLCγ2-P522R, but not in PLCγ2-WT expressing cells. Immunohistochemical analyses did not reveal changes in the number or morphology of microglia in the cortex of Plcγ2-P522R KI mice. However, the brain mRNA signature together with microglia-related PET imaging suggested enhanced microglial functions in Plcγ2-P522R KI mice. Conclusion The AD-associated protective Plcγ2-P522R variant promotes protective functions associated with TREM2 signaling. Our findings provide further support for the idea that pharmacological modulation of microglia via TREM2-PLCγ2 pathway-dependent stimulation may be a novel therapeutic option for the treatment of AD.

scholarly journals Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner

2013 ◽  
Vol 79 (7) ◽  
pp. 2328-2335 ◽  
Author(s):  
Ippei Hironaka ◽  
Tadayuki Iwase ◽  
Shinya Sugimoto ◽  
Ken-ichi Okuda ◽  
Akiko Tajima ◽  
...  
Keyword(s):  
Stationary Phase ◽  
Growth Phase ◽  
Cell Function ◽  
Immune Cell ◽  
Dependent Manner ◽  
T Helper 17 ◽  
Content Type ◽  
Cell Functions ◽  
Atp Secretion ◽  
Enterococcus Gallinarum

ABSTRACTATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported thatEnterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci,Enterococcus mundtiisecreted the greatest amount of ATP (>2 μM/108cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion fromE. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phaseE. mundtiiandEnterococcus faecaliscells secrete ATP more efficiently than stationary-phase cells. Other bacteria, includingPseudomonas aeruginosa,Escherichia coli, andStaphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function.

scholarly journals Mismatch of Glucose Allocation between Different Life Functions in the Transition Period of Dairy Cows

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1028 ◽  
Author(s):  
Jonas Habel ◽  
Albert Sundrum
Keyword(s):  
Immune Cell ◽  
Transition Period ◽  
Receptor Expression ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Immune Functions ◽  
Somatotropic Axis ◽  
Cell Functions ◽  
Glucocorticoid Response ◽  
Proliferation And Differentiation

Immune cell functions such as phagocytosis and synthesis of immunometabolites, as well as immune cell survival, proliferation and differentiation, largely depend on an adequate availability of glucose by immune cells. During inflammation, the glucose demands of the immune system may increase to amounts similar to those required for high milk yields. Similar metabolic pathways are involved in the adaptation to both lactation and inflammation, including changes in the somatotropic axis and glucocorticoid response, as well as adipokine and cytokine release. They affect (i) cell growth, proliferation and activation, which determines the metabolic activity and thus the glucose demand of the respective cells; (ii) the overall availability of glucose through intake, mobilization and gluconeogenesis; and (iii) glucose uptake and utilization by different tissues. Metabolic adaptation to inflammation and milk synthesis is interconnected. An increased demand of one life function has an impact on the supply and utilization of glucose by competing life functions, including glucose receptor expression, blood flow and oxidation characteristics. In cows with high genetic merits for milk production, changes in the somatotropic axis affecting carbohydrate and lipid metabolism as well as immune functions are profound. The ability to cut down milk synthesis during periods when whole-body demand exceeds the supply is limited. Excessive mobilization and allocation of glucose to the mammary gland are likely to contribute considerably to peripartal immune dysfunction.

Efficient Binding, but Moderate Modulation, of Human Dendritic Cell Functions by Milatuzumab, a Humanized Anti-CD74 Monoclonal Antibody

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2649-2649 ◽  
Author(s):  
Xiaochuan Chen ◽  
Chien-Hsing Chang ◽  
David Goldenberg
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cell Viability ◽  
Antigen Presenting Cells ◽  
Lymphocytic Leukemia ◽  
Dependent Manner ◽  
Immune Functions ◽  
Cell Functions ◽  
Antigen Presenting

Abstract Milatuzumab (hLL1, Immunomedics, Inc.), a humanized anti-CD74 immunoglobulin-G monoclonal antibody (MAb), has been shown to have therapeutic activity against CD74-expressing B-cell malignancies in vitro and in xenografts models, and is in clinical evaluation as a therapeutic MAb for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Since it is unclear whether this MAb has any effects on human antigen-presenting cells that express CD74, we investigated the binding efficiency, viability, and functional modulation of human dendritic cells (DC), the professional and most potent antigen-presenting cells, exposed to milatuzumab. We found that milatuzumab bound efficiently with B cells, monocytes, and different subsets of blood DCs including myeloid DC1 (BDCA-1+), myeloid DC2 (BDCA-3+) and plasmacytoid DC (BDCA-2+) in human PBMC, as well as with monocyte-derived immature DCs, but not LPS-matured DCs. The side-by-side comparative cytotoxicity assay showed that milatuzumab, in the presence of a second antibody for cross-linking (GAH, the F(ab′)2 of goat anti-human IgG Fcgamma-specific), dramatically reduced the cell viability of Daudi B-lymphoma cells, but did not influence the cell viability or induce apoptosis in monocyte-derived DCs, even at high concentations up to 50 μg/ml. At the concentrations ranging from 0.05 to 5 μg/ml, milatuzumab upregulated the expression of the antigen-presenting molecule, HLA-DR, and costimulatory molecules, CD54 and CD86, in human monocyte-derived DCs in a moderate, but dose-dependent manner, suggesting that milatuzumab could enhance DC constitutive maturation. Although this effect was not reflected by an enhanced T-cell expansion, as shown by unaltered CFSE-low, -medium, and –high peaks in total and CD4+ and CD4− T cells, milatuzumab-treated DCs could moderately promote the differentiation of CD4+ naïve T cells toward more Th1 effector cells, suggesting that milatuzumab can modulate DC functions, inducing the polarization and differentiation of functional Th cells. These data highlight the prospects of milatuzumab as a novel immunotherapeutic agent that possesses not only direct anti-proliferative effects against CD74+ hematological malignancies, but also some regulatory effects on DC-mediated immune functions, and no cytotoxic effect on DCs.

Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation

2005 ◽  
Vol 289 (5) ◽  
pp. L856-L866 ◽  
Author(s):  
Delphine C. Malherbe ◽  
Veit J. Erpenbeck ◽  
Soman N. Abraham ◽  
Erika C. Crouch ◽  
Jens M. Hohlfeld ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immune Cell ◽  
Allergic Inflammation ◽  
Surfactant Protein ◽  
Mast Cell Degranulation ◽  
Surfactant Protein D ◽  
Dependent Manner ◽  
Cell Functions ◽  
Pulmonary Surfactant Proteins

Mast cells play a key role in allergy and asthma. They reside at the host-environment interface and are among the first cells to make contact with inhaled microorganisms and particulate antigens. Pulmonary surfactant proteins A and D (SP-A and SP-D) function in lung host defense by enhancing microbe phagocytosis and mediating other immune cell functions, but little is known about their effects on mast cells. We hypothesized that SP-A and/or SP-D modulate IgE-dependent mast cell functions. Pollen starch granules (PSG) extracted from Dactylis glomerata and coated with trinitrophenol (TNP) were used as a model of an inhaled organic particulate allergen. Our data revealed that SP-D inhibited by 50% the release of β-hexosaminidase by peritoneal mast cells sensitized with IgE anti-TNP and stimulated with TNP-PSG. In contrast, SP-A had no effect. Furthermore, SP-D aggregated PSG in a dose-dependent manner, and this aggregation was mediated by SP-D's carbohydrate recognition domain. A single arm SP-D mutant (RrSP-Dser15,20) neither aggregated PSG nor inhibited degranulation, suggesting that multimerization of SP-D is required for maximal PSG aggregation and inhibition of PSG-induced mast cell degranulation. This study is the first to demonstrate that SP-D modulates IgE-mediated mast cell functions, which are important in asthma and allergic inflammation.

scholarly journals Regulation of Immune Functions by Non-Neuronal Acetylcholine (ACh) via Muscarinic and Nicotinic ACh Receptors

2021 ◽  
Vol 22 (13) ◽  
pp. 6818
Author(s):  
Masato Mashimo ◽  
Yasuhiro Moriwaki ◽  
Hidemi Misawa ◽  
Koichiro Kawashima ◽  
Takeshi Fujii
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Functions ◽  
Cell Functions ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Cellular And Humoral Immunity ◽  
Ach Receptors

Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.

scholarly journals Hypoxia modulates human mast cell adhesion to hyaluronic acid

2021 ◽  
Author(s):  
Joanna Pastwińska ◽  
Aurelia Walczak-Drzewiecka ◽  
Elżbieta Kozłowska ◽  
Enjuro Harunari ◽  
Marcin Ratajewski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Hyaluronic Acid ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Immune Cell ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Cell Functions ◽  
Extracellular Matrix Components

AbstractHypoxia is an inherent factor in the inflammatory process and is important in the regulation of some immune cell functions, including the expression of mast cell pro- and anti-inflammatory mediators. Hypoxia also influences cell adhesion to the extracellular matrix (ECM). Hyaluronic acid is one of the major components of the ECM that is involved in inflammatory and tissue regeneration processes in which mast cells play a prominent role. This prompted us to investigate the effects of hypoxia on the expression of hyaluronic acid receptors in mast cells and mast cell adhesion to this ECM component. We found that human LAD2 mast cells spontaneously adhered to hyaluronic acid in a CD44-dependent manner and that reduced oxygen concentrations inhibited or even completely abolished this adhesion process. The mechanism of hypoxia downregulation of mast cell adhesion to hyaluronic acid did not involve a decrease in CD44 expression and hyaluronidase-mediated degradation of adhesion substrates but rather conformational changes in the avidity of CD44 to hyaluronic acid. Hypoxia-mediated regulation of mast cell adhesion to extracellular matrix components might be involved in the pathogenic accumulation of mast cells observed in the course of certain diseases including rheumatoid arthritis and cancer.

scholarly journals Supplemental 25-hydroxycholecalciferol Alleviates Inflammation and Cardiac Fibrosis in Hens

2020 ◽  
Vol 21 (21) ◽  
pp. 8379
Author(s):  
Pao-Chia Chou ◽  
Yu-Hui Chen ◽  
Thau-Kiong Chung ◽  
Rosemary L. Walzem ◽  
Lih-Shiuh Lai ◽  
...  
Keyword(s):  
Er Stress ◽  
Feed Intake ◽  
Cardiac Fibrosis ◽  
Feed Conversion ◽  
Broiler Breeder ◽  
Beneficial Effects ◽  
Sequestosome 1 ◽  
Breeder Hens ◽  
Broiler Breeder Hens ◽  
25 Hydroxycholecalciferol

Broiler breeder hens with efficient feed conversion rate under restricted feed intake (R-hens) or allowed unlimited access to feed (Ad-hens) progressed with cardiac functional failure and suffered early sudden death. A supplement of 69 μg 25-hydroxycholecalciferol (25-OH-D3)/kg feed improved heart health and rescued livability in both R- and Ad-hens throughout laying stage (26–60 wks). Improvements occurred through cardiac hypertrophic remodeling, reduced arrhythmias, and pathological cues. Here, we further demonstrated consistently decreased circulating and cardiac IL-6 and IL-1β levels in conjunction with reduced cardiac chemoattraction and leukocyte infiltration by 25-OH-D3 in Ad-hens and in R-hens at later time points (35 and 47 wks) (p < 0.05). Supplemental 25-OH-D3 also ameliorated cardiac fibrosis, endoplasmic reticulum (ER) stress, and autophagy, mostly in Ad-hens, as both collagen content and expression of COL3A1, as well as CCAAT box binding enhancer homologous protein (CHOP) and activating transcription factor 6 (ATF6), were consistently decreased, and suppression of microtubule-associated protein 1 light Chain 3 beta (LC3B) and Sequestosome 1 (SQSTM1) was rescued at 35 and 47 wks (p < 0.05). Vitamin D receptor-NF-κB signaling was shown to mediate these beneficial effects. The present results demonstrate that ER stress and autophagic processes along the sequence from inflammation to fibrotic changes contribute to pathological cardiac remodeling and functional compromise by Ad-feed intake. 25-OH-D3 is an effective anti-inflammatory and anti-fibrotic supplement to ameliorate cardiac pathogenesis in broiler breeder hens.

scholarly journals Peptoanaerobacter stomatis Primes Human Neutrophils and Induces Granule Exocytosis

2017 ◽  
Vol 85 (7) ◽  
Author(s):  
E. Jimenez Flores ◽  
S. Tian ◽  
M. Sizova ◽  
S. S. Epstein ◽  
R. J. Lamont ◽  
...  
Keyword(s):  
Respiratory Burst ◽  
Immune Cell ◽  
Periodontal Diseases ◽  
Gingival Tissue ◽  
Human Neutrophils ◽  
Periodontal Pathogens ◽  
Bacterial Killing ◽  
Pathogenic Potential ◽  
Content Type ◽  
Superoxide Release

ABSTRACT Peptoanaerobacter stomatis is a newly appreciated taxon associated with periodontal diseases; however, little is known about the organism's pathogenic potential or its interaction with the host immune response. Neutrophils are the most abundant innate immune cell present in the gingival tissue and function to constrain the oral microbial challenge. However, some periodontal pathogens have developed strategies to evade phagocytosis and killing by neutrophils. Therefore, to begin to understand the role of P. stomatis in periodontitis, we studied its interactions with human neutrophils. Our data showed that after 30 min of incubation, neutrophils failed to engulf P. stomatis efficiently; however, when P. stomatis was internalized, it was promptly eradicated. P. stomatis challenge induced a robust intracellular respiratory burst; however, this response did not contribute to bacterial killing. Minimal superoxide release was observed by direct bacterial challenge; however, P. stomatis significantly increased N-formyl-methionyl-leucyl phenylalanine (fMLF)-stimulated superoxide release to an extent similar to that of cells primed with tumor necrosis factor alpha (TNF-α). When neutrophils were challenged with P. stomatis, 52% of the bacterium-containing phagosomes were enriched for the specific granule marker lactoferrin and 82% with the azurophil granule marker elastase. P. stomatis challenge stimulated exocytosis of the four neutrophil granule subtypes. Moreover, P. stomatis susceptibility to extracellular killing could be attributed to the exocytosis of antimicrobial components present in neutrophil granules. Priming neutrophils for an enhanced respiratory burst together with promoting granule content release could contribute to the chronic inflammation and tissue destruction that characterize periodontal diseases.

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