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Poultry Science Dec 2023This study aimed to evaluate the immunity of chickens up to 35 d subjected to posthatch fasting and supplementation with conjugated linoleic acid (CLA). A total of 320...
This study aimed to evaluate the immunity of chickens up to 35 d subjected to posthatch fasting and supplementation with conjugated linoleic acid (CLA). A total of 320 chicks were housed in a completely randomized design with a 2 × 2 factorial arrangement (0 or 12 h of fasting × 0.000 or 0.025% CLA in a prestarter diet), totaling 4 treatments (No-F-12 h; F-12 h; No-CLA; CLA) with 8 replicates of 10 birds each. The relative weights (% body weight) of the spleen and bursa were determined 12 h posthatch (Post-12 h) and then weekly. Immunoglobulin Y (IgY) titers against Newcastle disease virus (NDV) were measured by ELISA in the yolk sac contents Post-12 h and in the serum weekly. Hypersensitivity to phytohemagglutinin (PHA) inoculation was evaluated by toe-web swelling response on d 13 and 34, 4 times a day (after 3 h, 6 h, 12 h, and 24 h inoculation, respectively, PHA-3 h, PHA-6 h, PHA-12 h, and PHA-24 h). The data were subjected to analysis of variance (P < 0.05). F-12h reduced the Post-12 h relative weight of the spleen, and CLA reduced the relative weight of the bursa at this stage and at 28 d. At 13 d, F-12 h reduced PHA-3 h, whereas PHA-12 h was increased by CLA. At 34 d, CLA reduced PHA-3 h. A greater reaction was observed in the No-F-12 h-CLA chicks, for the PHA-24 h. In the Post-12 h evaluation, F-12h reduced, whereas CLA increased NDV-specific IgY titers in the yolk sac. No-F-12 h-No-CLA chicks had the lowest serum titers. At 21 d, F-12 h-CLA chicks exhibited the highest serum titers. Titers were higher in the F-12 h-No-CLA chicks, when compared to other treatments. At 28 d, fasting reduced the titers. In conclusion, F-12 h and CLA accelerated the transfer of immunoglobulins from the yolk sac to the serum. F-12 h impairs cellular immunity, whereas CLA favors it.
Topics: Animals; Chickens; Linoleic Acids, Conjugated; Immunity, Humoral; Diet; Fasting; Animal Feed
PubMed: 37926012
DOI: 10.1016/j.psj.2023.103167 -
Molecules (Basel, Switzerland) Oct 2023Different communities around the world traditionally use L. for medicinal purposes, mainly for its anti-inflammatory, antinociceptive, and antioxidant properties; it is...
Different communities around the world traditionally use L. for medicinal purposes, mainly for its anti-inflammatory, antinociceptive, and antioxidant properties; it is used as an ingredient in teas or herbal medicines for the treatment of pain, inflammation, and immunological disorders. Several studies have been conducted that prove the immunomodulatory properties of this plant; however, it is not known whether the immunomodulatory properties of are mediated by its ability to modulate antigen-presenting cells (APCs) such as macrophages (MØs) and dendritic cells (DCs) (through polarization or the maturation state, respectively). Different polar and non-polar extracts and fractions were prepared from the aerial part of . Their cytotoxic and immunomodulatory effects were first tested on human peripheral blood mononuclear cells (PBMCs) and phytohemagglutinin (PHA)-stimulated PBMCs, respectively, via an MTT assay. Then, the non-cytotoxic plant extracts and fractions that showed the highest immunomodulatory activity were selected to evaluate their effects on human MØ polarization and DC maturation (cell surface phenotype and cytokine secretion) through multiparametric flow cytometry. Finally, the chemical compounds of the extract that showed the most significant immunomodulatory effects on human APCs were identified using gas chromatography coupled with mass spectrometry. The petroleum ether extract and the ethyl acetate and hydroalcoholic fractions obtained from showed low cytotoxicity and modulated the PHA-stimulated proliferation of PBMCs. Furthermore, the petroleum ether extract induced M2 polarization or a hybrid M1/M2 phenotype in MØs and a semi-mature status in DCs, regardless of exposure to a maturation stimulus. The immunomodulatory activity of the non-polar (petroleum ether) extract of on human PBMC proliferation, M2 polarization of MØs, and semi-mature status in DCs might be attributed to the low-medium polarity components in the extract, such as phytosterol terpenes and fatty acid esters.
Topics: Humans; Bidens; Leukocytes, Mononuclear; Gas Chromatography-Mass Spectrometry; Plant Extracts; Anti-Inflammatory Agents; Solvents; Macrophages; Phenotype; Dendritic Cells
PubMed: 37894572
DOI: 10.3390/molecules28207094 -
Current Therapeutic Research, Clinical... 2023Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood.
BACKGROUND
Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood.
OBJECTIVES
This study evaluated the influence of bovine colostrum products, a whey product, or their combinations with other natural products on human peripheral blood mononuclear cells' (PBMC) ability to produce cytokines upon activation.
METHODS
PBMCs were pretreated with ultrafiltered colostrum, nano-filtered bovine colostrum, egg yolk extract, a botanical blend, colostrum + egg yolk extract, colostrum + egg yolk + botanical blend, and fermented whey and then stimulated with lipopolysaccharide or phytohemagglutinin. Cytokine production was measured by the Luminex assay.
RESULTS
All study products demonstrated immunomodulatory properties by regulating cytokines production by activated PBMCs. Ultrafiltered colostrum alone displayed the highest immune stimulatory activity. It stimulated proinflammatory cytokine production by lipopolysaccharide-activated PBMCs and suppressed cytokine production by phytohemagglutinin-activated cells. Other study products mainly suppressed cytokine release by both cell types. The immunomodulatory properties depended upon the dose of the products used in the study.
CONCLUSIONS
All tested products modulated innate and adaptive immune cell activities. Most of the products demonstrated anti-inflammatory properties, except ultrafiltered colostrum, which stimulated the lipopolysaccharide-activated PBMC production of inflammatory cytokines. These products can be potentially used to support overall immune health.
PubMed: 37885900
DOI: 10.1016/j.curtheres.2023.100720 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250 -
Frontiers in Nutrition 2023Individuals with obesity and/or type 2 diabetes are at higher risk of infection and have worse prognoses compared to healthy individuals. Several factors may influence...
The nutrition and immunity (nutrIMM) study: protocol for a non-randomized, four-arm parallel-group, controlled feeding trial investigating immune function in obesity and type 2 diabetes.
INTRODUCTION
Individuals with obesity and/or type 2 diabetes are at higher risk of infection and have worse prognoses compared to healthy individuals. Several factors may influence immune responses in this population, including high adiposity, hyperglycemia, and unhealthy dietary habits. However, there is insufficient data on the independent or clustered contribution of these factors to obesity-related immune dysfunction, especially accounting for dietary intake. This study aims to establish the independent contribution of obesity and hyperglycemia to immune dysfunction independent of diet in adults with and without obesity with or without type 2 diabetes.
METHODS
The Nutrition and Immunity (nutrIMM) study is a single-centre, non-randomized, four-arm, parallel-group, controlled feeding trial. It will enroll adults without obesity (Lean-NG) and with obesity and three metabolic phenotypes of normoglycemia, glucose intolerance, and type 2 diabetes. Participants will be assigned to one of four groups and will consume a standard North American-type diet for 4 weeks. The primary outcomes are plasma concentration of C-reactive protein and concentration of interleukin-2 secreted upon stimulation of T cells with phytohemagglutinin.
DISCUSSION
This will be the first controlled feeding study examining the contribution of obesity, hyperglycemia, and diet on systemic inflammation, immune cell phenotype, and function in adults of both sexes. Results of this clinical trial can ultimately be used to develop personalized dietary strategies to optimize immune function in individuals with obesity with different immune and metabolic profiles.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT04291391.
PubMed: 37727636
DOI: 10.3389/fnut.2023.1243359 -
European Journal of Medical Research Aug 2023We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral...
BACKGROUND
We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH).
METHODS
Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity.
RESULTS
Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses.
CONCLUSION
These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.
Topics: Humans; Hydrocortisone; Interleukin-17; Interleukin-6; Lipopolysaccharides; Mifepristone; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha; Immunosuppression Therapy; Interferon-gamma
PubMed: 37644600
DOI: 10.1186/s40001-023-01222-3 -
Plants (Basel, Switzerland) Aug 2023α-amylase inhibitor (α-AI) is a protein that has recently gained commercial interest, as it inhibits mammalian α-amylase activity, reducing the absorption of dietary...
α-amylase inhibitor (α-AI) is a protein that has recently gained commercial interest, as it inhibits mammalian α-amylase activity, reducing the absorption of dietary carbohydrates. Numerous studies have reported the efficacy of preparations based on this protein on the control of glycaemic peaks in type-2 diabetes patients and in overweight subjects. A positive influence on microbiota regulation has also been described. In this work, ten insufficiently studied Italian cultivars were screened for α-amylase- and α-glucosidase-inhibiting activity, as well as for the absence of antinutritional compounds, such as phytohemagglutinin (PHA). All the cultivars presented α-glucosidase-inhibitor activity, while α-AI was missing in two of them. Only the Nieddone cultivar (ACC177) had no haemagglutination activity. In addition, the partial nucleotide sequence of the α-AI gene was identified with the degenerate hybrid oligonucleotide primer (CODEHOP) strategy to identify genetic variability, possibly linked to functional α-AI differences, expression of the α-AI gene, and phylogenetic relationships. Molecular studies showed that α-AI was expressed in all the cultivars, and a close similarity between the Pisu Grogu and Fasolu cultivars' α-AI and α-AI-4 isoform emerged from the comparison of the partially reconstructed primary structures. Moreover, mechanistic models revealed the interaction network that connects α-AI with the α-amylase enzyme characterized by two interaction hotspots (Asp38 and Tyr186), providing some insights for the analysis of the α-AI primary structure from the different cultivars, particularly regarding the structure-activity relationship. This study can broaden the knowledge about this class of proteins, fuelling the valorisation of Italian agronomic biodiversity through the development of commercial preparations from legume cultivars.
PubMed: 37631130
DOI: 10.3390/plants12162918 -
Bioengineering (Basel, Switzerland) Aug 2023Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment....
Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment. Three-dimensional (3D) culture can enhance these properties, and large-scale expansion using a bioreactor can reduce manufacturing costs. Three lots of MTFs were obtained from umbilical cord MSCs produced by either monolayer culture (Monol MTF) or using a 3D microcarrier in a spinner flask dynamic system (Bioreactor MTF). The resulting MTFs were tested and compared using anti-inflammatory potency assays in two different systems: (1) a phytohemagglutinin-activated peripheral blood mononuclear cell (PBMNC) system and (2) a lipopolysaccharide (LPS)-activated macrophage system. Cytokine expression by macrophages was measured via RT-PCR. The production costs of hypothetical units of anti-inflammatory effects were calculated using the percentage of TNF-α inhibition by MTF exposure. Bioreactor MTFs had a higher inhibitory effect on TNF ( < 0.01) than monolayer MTFs ( < 0.05). The anti-inflammatory effect of Bioreactor MTFs on IL-1β, TNF-α, IL-8, IL-6, and MIP-1 was significantly higher than that of monolayer MTFs. The production cost of 1% inhibition of TNF-α was 11-40% higher using monolayer culture compared to bioreactor-derived MTFs. A 3D dynamic culture was, therefore, able to produce high-quality MTFs, with robust anti-inflammatory properties, more efficiently than monolayer static systems.
PubMed: 37627815
DOI: 10.3390/bioengineering10080930 -
Biomolecules Jul 2023Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light... (Review)
Review
Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, bronchi, epidermis, esophagus, breast, stomach, ilium, colorectum, gall bladder, urinary bladder, seminal vesicles ovarian epithelia, endometrium, thymus, spleen, and lymphocytes. They are upregulated on immune cells upon activation by proinflammatory cytokines, anti-CD3 antibodies, antibiotics (e.g., ionomycin), phytohemagglutinin, retinoic acid, and phorbol myristate acetate. Their density on the cell surface remains high as long as the cells remain in an activated state. After activation-induced upregulation, the Face-2 molecules undergo homo- and hetero-dimerization (Face-3 and Face-4). Alterations in the redox environment promote dimerization. Heterodimerization can occur among and between the alleles of different haplotypes. The glycosylation of these variants differ from that of Face-1, and they may occur with bound exogenous peptides. Spontaneous arthritis occurs in HLA-B27+ mice lacking B2m (HLA-B27+ B2m-/-) but not in HLA-B27+ B2m+/- mice. The mice with HLA-B27 in Face-2 spontaneous configuration develop symptoms such as changes in nails and joints, hair loss, and swelling in paws, leading to ankyloses. Anti-HC-specific mAbs delay disease development. Some HLA-I polyreactive mAbs (MEM series) used for immunostaining confirm the existence of B2m-free variants in several cancer cells. The upregulation of Face-2 in human cancers occurs concomitantly with the downregulation of intact HLAs (Face-1). The HLA monomeric and dimeric variants interact with inhibitory and activating ligands (e.g., KIR), growth factors, cytokines, and neurotransmitters. Similarities in the amino acid sequences of the HLA-I variants and HLA-II β-chain suggest that Face-2 could be the progenitor of both HLA classes. These findings may support the recognition of these variants as a neo-HLA class and proto-HLA.
Topics: Female; Male; Humans; Animals; Mice; HLA-B27 Antigen; HLA Antigens; Cell Membrane; Cytokines; Anti-Bacterial Agents; Antibodies, Monoclonal
PubMed: 37627243
DOI: 10.3390/biom13081178 -
Heliyon Aug 2023Outer membrane protein W (OmpW) is a less-known antigen with potential immunogenic properties. The epitopes of this protein are not well-identified yet. Therefore, in...
Outer membrane protein W (OmpW) is a less-known antigen with potential immunogenic properties. The epitopes of this protein are not well-identified yet. Therefore, in the present study, B- and T-cell epitopes of OmpW were found using comprehensive in silico and partially in vitro studies. The T-cell (both class-I and class-II) and B-cell (both linear and conformational) epitopes were predicted and screened through many bioinformatics approaches including the prediction of IFN-γ production, immunogenicity, toxicity, allergenicity, human similarity, and clustering. A single 15-mer epitopic peptide containing a linear B-cell and both classes of T-cell epitopes were found and used for further assays. For in vitro assays, patient- and healthy control-derived peripheral blood mononuclear cells were stimulated with the 15-mer peptide, Phytohemagglutinin, or medium alone, and cell proliferation and IFN-γ production assays were performed. The bioinformatics studies led to mapping OmpW epitopes and introducing a 15-mer peptide. In vitro assays to some extent showed its potency in cell proliferation but not in IFN-γ induction, although the responses were not very expressive and faced some questions/limitations. In general, in the current study, we mapped the most immunogenic epitopes of OmpW that may be used for future studies and also assayed one of these epitopes in vitro, which was shown to have an immunogenicity potential. However, the induced immune responses were not strong which suggests that the present peptide needs a series of biotechnological manipulations to be used as a potential vaccine candidate. More studies in this field are recommended.
PubMed: 37560650
DOI: 10.1016/j.heliyon.2023.e18614