scholarly journals Bacterial Endotoxins and Their Role in Periparturient Diseases of Dairy Cows: Mucosal Vaccine Perspectives

Dairy ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 61-90
Author(s):  
Emily F. Eckel ◽  
Burim N. Ametaj

During the periparturient period there is a significant increase in the incidence of multiple metabolic and infectious diseases in dairy cows. Dairy cows are fed high-grain diets immediately after calving to support production of large amounts of milk. Mounting evidence indicates these types of diets are associated with the release of high amounts of endotoxins in the rumen fluid. If infected, the udder and uterus additionally become important sources of endotoxins during the postpartum period. There is increasing evidence that endotoxins translocate from rumen, uterus, or udder into the systemic circulation and trigger chronic low-grade inflammatory conditions associated with multiple diseases including fatty liver, mastitis, retained placenta, metritis, laminitis, displaced abomasum, milk fever, and downer cow syndrome. Interestingly, endotoxin-related diseases are triggered by a bacterial component and not by a specific bacterium. This makes prevention of these type of diseases different from classical infectious diseases. Prevention of translocation of endotoxins into the host systemic circulation needs to take priority and this could be achieved with a new approach: mucosal vaccination. In this review article, we discuss all the aforementioned issues in detail and also report some of our trials with regards to mucosal vaccination of periparturient dairy cows.

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246422
Author(s):  
Rui Tada ◽  
Miki Ogasawara ◽  
Daisuke Yamanaka ◽  
Yasuhiro Sakurai ◽  
Yoichi Negishi ◽  
...  

Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.


2020 ◽  
Vol 20 (9) ◽  
pp. 1523-1530
Author(s):  
Murat Dabak ◽  
Durrin O. Dabak ◽  
Tuncay Kuloglu ◽  
Ersoy Baydar ◽  
Hakan Bulut ◽  
...  

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.


Dairy ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 40-64
Author(s):  
Eduardo Barahona Rosales ◽  
Burim N. Ametaj

Postpartum uterine diseases are common in dairy cows and are a great concern for the dairy industry as they are associated with various consequences, including lower fertility, lower milk yield, and an overall negative impact on the host health. An infected uterus is a source of bacterial compounds and cytokines that spill into the systemic circulation, spreading inflammation to other organs. In this review article, we discuss a short overview of the anatomy of the reproductive tract of dairy cows and several infectious diseases of the uterus including metritis, endometritis, and pyometra. Additionally, we discuss the microbiome of the reproductive tract in health and during uterine diseases. As well, diagnostic criteria for metritis and endometritis and contributing factors for increased susceptibility to metritis infection are important topics of this review. To better understand how the uterus and reproductive tract respond to bacterial pathogens, a section of this review is dedicated to immunity of the reproductive tract. Both the innate and adaptive immunity systems are also discussed. We conclude the review with a factual discussion about the current treatments of uterine diseases and the new developments in the area of application of probiotics for uterine health. Mechanisms of actions of probiotics are discussed in detail and also some applications to prevent uterine infections in dairy cows are discussed.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.


2021 ◽  
Author(s):  
Kaihe Xiang ◽  
Xiaoyu Hu ◽  
Ruiying Mu ◽  
Shuang Li ◽  
Ying Wang ◽  
...  

Abstract Backgroud: Mastitis is the most serious disease endangering animal husbandry, especially dairy farming. Clinical investigations indicated that cows suffering from ketosis have a higher probability of mastitis. Rumen microbiota is closely related to ruminant health. However, it is not clear what role it plays in this process.Results: The microbiota in rumen fluid and milk from ketosis cows were determined by 16S rRNA gene sequencing. The results showed that the richness of bacterial community both in rumen and milk were changed in ketosis cows. The abundance of genus Prevotella, Ruminococcus, Succinivibrionaceae_UCG-001 and Streptococcus in rumen fluid from ketosis cows decreased significantly and were negatively correlated with blood BHBA and milk SCC. In contrast, the abundance of genus Luteimonas, Thermomonas, Christensenellaceae_R-7_group, Rikenellaceae_RC9_gut_group, NK4A214_group, Paracoccus, Acetitomaculum, Prevotellaceae_UCG-003, Deinococcus, Saccharofermentans and Butyrivibrio in rumen fluid from ketosis cows increased significantly and were positively correlated with blood BHBA and milk SCC. In addition, the abundance of F082 and Thermomonas were increased, while the abundance of genus Acinetobacter and UCG-005 were reduced both in milk and rumen fluid in ketosis cows than healthy cows. Conclusions: Ketosis in dairy cows is capable of inducing mastitis. The rumen microbiota of ketotic cows changed significantly and is associated with the development of mastitis. Targeting rumen microbiota regulation may be a promising strategy to prevent metabolism disorder and its secondary diseases in dairy cows.


Author(s):  
Aiswarya Anilkumar Ajitha ◽  
Sri SivaKumar ◽  
Gayathri Viswanathan ◽  
Sabulal Baby ◽  
Prabath Gopalakrishnan Biju

Background: Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles helps to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action. Objective: Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles. Method: PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material is detailed herein. Results: Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 μg/mL in culture. Biocompatibility and absence of toxicity was determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac. Conclusion: In this paper we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.


1990 ◽  
Vol 70 (2) ◽  
pp. 731-734 ◽  
Author(s):  
A. S. ATWAL ◽  
J. D. ERFLE

Large day-to-day variations in milk fat, particularly for the morning milkings, were observed in 36 Holstein cows. Changes in percent fat were gradual and produced wavelike patterns in a number of instances. Supplemental feeding of long hay had no effect on acetate/propionate ratio in rumen fluid, daily milk yield or weighted milk fat percentage. Key words: Dairy cows, milk, fat depression, hay


2021 ◽  
Vol 17 (3) ◽  
pp. e1009324
Author(s):  
Lucas dos Santos Dias ◽  
Hannah E. Dobson ◽  
Brock Kingstad Bakke ◽  
Gregory C. Kujoth ◽  
Junfeng Huang ◽  
...  

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kathleen L. Vincent ◽  
Patrice A. Frost ◽  
Massoud Motamedi ◽  
Edward J. Dick ◽  
Jingna Wei ◽  
...  

Vaginal mucosal surfaces naturally offer some protection against sexually transmitted infections (STIs) including Human Immunodeficiency Virus-1, however topical preventative medications or vaccine designed to boost local immune responses can further enhance this protection. We previously developed a novel mucosal vaccine strategy using viral vectors integrated into mouse dermal epithelium to induce virus-specific humoral and cellular immune responses at the site of exposure. Since vaccine integration occurs at the site of cell replication (basal layer 100-400 micrometers below the surface), temporal epithelial thinning during vaccine application, confirmed with high resolution imaging, is desirable. In this study, strategies for vaginal mucosal thinning were evaluated noninvasively using optical coherence tomography (OCT) to map reproductive tract epithelial thickness (ET) in macaques to optimize basal layer access in preparation for future effective intravaginal mucosal vaccination studies. Twelve adolescent female rhesus macaques (5-7kg) were randomly assigned to interventions to induce vaginal mucosal thinning, including cytobrush mechanical abrasion, the chemical surfactant spermicide nonoxynol-9 (N9), the hormonal contraceptive depomedroxyprogesterone acetate (DMPA), or no intervention. Macaques were evaluated at baseline and after interventions using colposcopy, vaginal biopsies, and OCT imaging, which allowed for real-time in vivo visualization and measurement of ET of the mid-vagina, fornices, and cervix. P value ≤0.05 was considered significant. Colposcopy findings included pink, rugated tissue with variable degrees of white-tipped, thickened epithelium. Baseline ET of the fornices was thinner than the cervix and vagina (p<0.05), and mensing macaques had thinner ET at all sites (p<0.001). ET was decreased 1 month after DMPA (p<0.05) in all sites, immediately after mechanical abrasion (p<0.05) in the fornix and cervix, and after two doses of 4% N9 (1.25ml) applied over 14 hrs in the fornix only (p<0.001). Histological assessment of biopsied samples confirmed OCT findings. In summary, OCT imaging allowed for real time assessment of macaque vaginal ET. While varying degrees of thinning were observed after the interventions, limitations with each were noted. ET decreased naturally during menses, which may provide an ideal opportunity for accessing the targeted vaginal mucosal basal layers to achieve the optimum epithelial thickness for intravaginal mucosal vaccination.


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