scholarly journals Oligosaccharide equine feed supplement, Immulix, has minor impact on vaccine responses in mice

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ida Wang Henriksen ◽  
Josue Leonardo Castro Mejia ◽  
Caroline Martha Junker Mentzel ◽  
Frederikke Lindenberg ◽  
Axel Kornerup Hansen

AbstractSeveral mammalian species are vaccinated in early life, but little is known about the effect of diet on vaccine response. Oligosaccharides are increasingly proposed as dietary supplement for young individuals due to their anti-inflammatory potential elicited through modulation of gut microbiota (GM). Also, diet, e.g. the size of the fat fraction, is known to modulate the GM. We tested if an oligosaccharide diet (Immulix) and/or increased dietary fat content affected antibody titers to a tetanus vaccine in 48 BALB/cJTac mice through GM modulation. Female mice had significantly higher IgG titers with higher variation compared to male mice. The effects of Immulix and/or increased fat content were minor. Immulix negatively affected IgG titers in male mice four weeks after secondary vaccination but upregulated Il1b gene expression in the spleen. Immulix had a downregulating effect on expression of Cd4 and Foxp3 in ileum only if the mice were fed the diet with increased fat. The diet with increased dietary fat increased Il1b but decreased Cd8a gene expression in the spleen. Immulix and diet affected GM composition significantly. Increased dietary fat content upregulated Lactobacillus animalis but downregulated an unclassified Prevotella spp. Immulix decreased Lactobacillales, Streptococcaceae and Prevotellaceae but increased Bacteroides. It is concluded that in spite of some minor influences on immune cell markers, cytokines and IgG titers Immulix feeding or increased dietary fat content did not have any biologically relevant effects on tetanus vaccine responses in this experiment in mice.

2022 ◽  
Vol 12 ◽  
Author(s):  
Annelene Govindsamy ◽  
Samira Ghoor ◽  
Marlon E. Cerf

Fetal programming refers to an intrauterine stimulus or insult that shapes growth, development and health outcomes. Dependent on the quality and quantity, dietary fats can be beneficial or detrimental for the growth of the fetus and can alter insulin signaling by regulating the expression of key factors. The effects of varying dietary fat content on the expression profiles of factors in the neonatal female and male rat heart were investigated and analyzed in control (10% fat), 20F (20% fat), 30F (30% fat) and 40F (40% fat which was a high fat diet used to induce high fat programming) neonatal rats. The whole neonatal heart was immunostained for insulin receptor, glucose transporter 4 (Glut4) and forkhead box protein 1 (FoxO1), followed by image analysis. The expression of 84 genes, commonly associated with the insulin signaling pathway, were then examined in 40F female and 40F male offspring. Maintenance on diets, varying in fat content during fetal life, altered the expression of cardiac factors, with changes induced from 20% fat in female neonates, but from 30% fat in male neonates. Further, CCAAT/enhancer-binding protein alpha (Cebpa) was upregulated in 40F female neonates. There was, however, differential expression of several insulin signaling genes in 40F (high fat programmed) offspring, with some tending to significance but most differences were in fold changes (≥1.5 fold). The increased immunoreactivity for insulin receptor, Glut4 and FoxO1 in 20F female and 30F male neonatal rats may reflect a compensatory response to programming to maintain cardiac physiology. Cebpa was upregulated in female offspring maintained on a high fat diet, with fold increases in other insulin signaling genes viz. Aebp1, Cfd (adipsin), Adra1d, Prkcg, Igfbp, Retn (resistin) and Ucp1. In female offspring maintained on a high fat diet, increased Cebpa gene expression (concomitant with fold increases in other insulin signaling genes) may reflect cardiac stress and an adaptative response to cardiac inflammation, stress and/or injury, after high fat programming. Diet and the sex are determinants of cardiac physiology and pathophysiology, reflecting divergent mechanisms that are sex-specific.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Babajide Ojo ◽  
Grace Gallucci ◽  
Jerry Ritchey ◽  
Winyoo Chowanadisai ◽  
Stephen Clarke ◽  
...  

Abstract Objectives Fiber-rich foods such as pinto beans (PB) may exhibit prebiotic effects by preventing early immunosuppression and gut permeability associated with the onset of insulin resistance (IR). Thus, this study evaluated the early protective effects of PB supplementation on the cecal gut microflora, tight-junction protein abundances, gut inflammatory markers and glucose homeostasis in mice fed either a control (C) or a high-fat, high sucrose (HFS). Methods Six-wk-old, male C57BL/6 J mice were randomly assigned to four groups (n = 12/group) and fed a control (C, 10% kcal fat, 10% kcal sucrose) or HFS (45% kcal fat, 20% kcal sucrose) diet with or without 10% (wt/wt) freeze-dried PB for 30 d. Measures include fasting blood glucose (FBG), cecal bacteria analyses by 16 S rDNA sequencing, gene expression of gut antimicrobial peptides and markers of inflammation in the distal ileum by qPCR, and expression of tight junction proteins, STAT3 and MHC II in the distal ileum by immunoblotting. Statistical analyses include the Kruskal-Wallis/Dunn's post-hoc test, and a 2-way ANOVA using factors of HFS and PB. Results FBG was increased by HFS (main effect, P = 0.0070) while PB decreased FBG by at least 13% (main effect, P = 0.046). In the cecum, the sulfide-producing bacteria family Desulfovibrionaceae (genus Bilophilia) was decreased (≤49%, P ≤ 0.022) in the PB-fed mice compared to their controls. In contrast, the short chain fatty acid-producing family Lachnospiraceae, was elevated by at least 47% (P ≤ 0.0043) in the PB-fed groups compared to their controls. We also observed a 3-fold decrease (P = 0.012) in Ifng gene expression in the HFS group compared to control, together with a decrease in the phosphorylation of STAT3 in the distal ileum (P = 0.045). On the other hand, PB supplementation increased pSTAT3 (main effect, P = 0.022), MHC II (≥66%, main effect, P = 0.0040), with a trend to upregulate occludin (P = 0.055). Moreover, antimicrobial peptide genes, Reg3β and Reg3γ, and Il10 were upregulated by PB (main effect, P < 0.0094). Finally, a negative correlation between the genus Bilophilia and MHC II (Spearman, ρ = −0.5747, P = 0.0033) was observed Conclusions PB supplementation modulated the gut microbiome regardless of dietary fat content, and upregulated MHC II in the distal ileum. These effects may be central to its potential to protect against diet-induced IR Funding Sources Northarvest Bean Growers Association.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.


Genetics ◽  
2021 ◽  
Author(s):  
Thomas D Brekke ◽  
Emily C Moore ◽  
Shane C Campbell-Staton ◽  
Colin M Callahan ◽  
Zachary A Cheviron ◽  
...  

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.


Author(s):  
Jack Arnold ◽  
Kevin Winthrop ◽  
Paul Emery

Abstract The coronavirus disease 2019 (COVID-19) vaccination will be the largest vaccination programme in the history of the NHS. Patients on immunosuppressive therapy will be among the earliest to be vaccinated. Some evidence indicates immunosuppressive therapy inhibits humoral response to the influenza, pneumococcal and hepatitis B vaccines. The degree to which this will translate to impaired COVID-19 vaccine responses is unclear. Other evidence suggests withholding MTX for 2 weeks post-vaccination may improve responses. Rituximab has been shown to impair humoral responses for 6 months or longer post-administration. Decisions on withholding or interrupting immunosuppressive therapy around COVID-19 vaccination will need to be made prior to the availability of data on specific COVID-19 vaccine response in these patients. With this in mind, this article outlines the existing data on the effect of antirheumatic therapy on vaccine responses in patients with inflammatory arthritis and formulates a possible pragmatic management strategy for COVID-19 vaccination.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein–protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoko Kato ◽  
Harumi Katsumata ◽  
Ayumu Inutsuka ◽  
Akihiro Yamanaka ◽  
Tatsushi Onaka ◽  
...  

AbstractMultiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shauna Kehoe ◽  
Katarina Jewgenow ◽  
Paul R. Johnston ◽  
Susan Mbedi ◽  
Beate C. Braun

AbstractIn vitro growth (IVG) of dormant primordial ovarian follicles aims to produce mature competent oocytes for assisted reproduction. Success is dependent on optimal in vitro conditions complemented with an understanding of oocyte and ovarian follicle development in vivo. Complete IVG has not been achieved in any other mammalian species besides mice. Furthermore, ovarian folliculogenesis remains sparsely understood overall. Here, gene expression patterns were characterised by RNA-sequencing in primordial (PrF), primary (PF), and secondary (SF) ovarian follicles from Felis catus (domestic cat) ovaries. Two major transitions were investigated: PrF-PF and PF-SF. Transcriptional analysis revealed a higher proportion in gene expression changes during the PrF-PF transition. Key influencing factors during this transition included the interaction between the extracellular matrix (ECM) and matrix metalloproteinase (MMPs) along with nuclear components such as, histone HIST1H1T (H1.6). Conserved signalling factors and expression patterns previously described during mammalian ovarian folliculogenesis were observed. Species-specific features during domestic cat ovarian folliculogenesis were also found. The signalling pathway terms “PI3K-Akt”, “transforming growth factor-β receptor”, “ErbB”, and “HIF-1” from the functional annotation analysis were studied. Some results highlighted mechanistic cues potentially involved in PrF development in the domestic cat. Overall, this study provides an insight into regulatory factors and pathways during preantral ovarian folliculogenesis in domestic cat.


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