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      Intravaginal Lactic Acid Bacteria Modulated Local and Systemic Immune Responses and Lowered the Incidence of Uterine Infections in Periparturient Dairy Cows

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          Abstract

          The objective of this investigation was to evaluate whether intravaginal infusion of a lactic acid bacteria (LAB) cocktail around parturition could influence the immune response, incidence rate of uterine infections, and the overall health status of periparturient dairy cows. One hundred pregnant Holstein dairy cows were assigned to 1 of the 3 experimental groups as follows: 1) one dose of LAB on wk -2 and -1, and one dose of carrier (sterile skim milk) on wk +1 relative to the expected day of parturition (TRT1); 2) one dose of LAB on wk -2, -1, and +1 (TRT2), and 3) one dose of carrier on wk -2, -1, and +1 (CTR). The LAB were a lyophilized culture mixture composed of Lactobacillus sakei FUA3089, Pediococcus acidilactici FUA3138, and Pediococcus acidilactici FUA3140 with a cell count of 10 8-10 9 cfu/dose. Blood samples and vaginal mucus were collected once a week from wk -2 to +3 and analyzed for content of serum total immunoglobulin G (IgG), lipopolysaccharide-binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and vaginal mucus secretory IgA (sIgA). Clinical observations including rectal temperature, vaginal discharges, retained placenta, displaced abomasum, and laminitis were monitored from wk -2 to +8 relative to calving. Results showed that intravaginal LAB lowered the incidence of metritis and total uterine infections. Intravaginal LAB also were associated with lower concentrations of systemic LBP, an overall tendency for lower SAA, and greater vaginal mucus sIgA. No differences were observed for serum concentrations of Hp, TNF, IL-1, IL-6 and total IgG among the treatment groups. Administration with LAB had no effect on the incidence rates of other transition cow diseases. Overall intravaginal LAB lowered uterine infections and improved local and systemic immune responses in the treated transition dairy cows.

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          Most cited references37

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          Innate immune recognition: mechanisms and pathways.

          The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large groups of microorganisms. Recognition of these patterns allows the innate immune system not only to detect the presence of an infectious microbe, but also to determine the type of the infecting pathogen. Pattern recognition receptors activate conserved host defense signaling pathways that control the expression of a variety of immune response genes.
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            Defining postpartum uterine disease in cattle.

            Uterine function is often compromised in cattle by bacterial contamination of the uterine lumen after parturition, and pathogenic bacteria often persist, causing uterine disease, a key cause of infertility in cattle. However, the definition or characterization of uterine disease frequently lacks precision or varies among research groups. The aim of the present paper was to provide clear clinical definitions of uterine disease that researchers could adopt. Puerperal metritis should be defined as an animal with an abnormally enlarged uterus and a fetid watery red-brown uterine discharge, associated with signs of systemic illness (decreased milk yield, dullness or other signs of toxemia) and fever > 39.5 degrees C, within 21 days after parturition. Animals that are not systemically ill, but have an abnormally enlarged uterus and a purulent uterine discharge detectable in the vagina, within 21 days post partum, may be classified as having clinical metritis. Clinical endometritis is characterised by the presence of purulent (> 50% pus) uterine discharge detectable in the vagina 21 days or more after parturition, or mucuopurulent (approximately 50% pus, 50% mucus) discharge detectable in the vagina after 26 days post partum. In the absence of clinical endometritis, a cow with subclinical endometritis is defined by > 18% neutrophils in uterine cytology samples collected 21-33 days post partum, or > 10% neutrophils at 34-47 days. Pyometra is defined as the accumulation of purulent material within the uterine lumen in the presence of a persistent corpus luteum and a closed cervix. In conclusion, we have suggested definitions for common postpartum uterine diseases, which can be readily adopted by researchers and veterinarians.
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              Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle.

              Uterine microbial disease affects half of all dairy cattle after parturition, causing infertility by disrupting uterine and ovarian function. Infection with Escherichia coli, Arcanobacterium pyogenes, and bovine herpesvirus 4 causes endometrial tissue damage. Toll-like receptors on endometrial cells detect pathogen-associated molecules such as bacterial DNA, lipids, and lipopolysaccharide (LPS), leading to secretion of cytokines, chemokines, and antimicrobial peptides. Chemokines attract neutrophils and macrophages to eliminate the bacteria, although persistence of neutrophils is associated with subclinical endometritis and infertility. Cows with uterine infections are less likely to ovulate because they have slower growth of the postpartum dominant follicle in the ovary, lower peripheral plasma estradiol concentrations, and perturbation of hypothalamic and pituitary function. The follicular fluid of animals with endometritis contains LPS, which is detected by the TLR4/CD14/LY96 (MD2) receptor complex on granulosa cells, leading to lower aromatase expression and reduced estradiol secretion. If cows with uterine disease ovulate, the peripheral plasma concentrations of progesterone are lower than those in normal animals. However, luteal phases are often extended in animals with uterine disease, probably because infection switches the endometrial epithelial secretion of prostaglandins from the F series to the E series by a phospholipase A2-mediated mechanism, which would disrupt luteolysis. The regulation of endometrial immunity depends on steroid hormones, somatotrophins, and local regulatory proteins. Advances in knowledge about infection and immunity in the female genital tract should be exploited to develop new therapeutics for uterine disease.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 April 2015
                2015
                : 10
                : 4
                : e0124167
                Affiliations
                [001]Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
                Facultad de Medicina, URUGUAY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BNA. Performed the experiments: QD JFO UF TL SMD. Analyzed the data: QD JFO. Contributed reagents/materials/analysis tools: BNA QD JFO UF TL SMD. Wrote the paper: QD BNA.

                Article
                PONE-D-14-41942
                10.1371/journal.pone.0124167
                4412408
                25919010
                589ffc7d-65b1-4a83-abaf-ee2740772f0c
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 17 September 2014
                : 10 March 2015
                Page count
                Figures: 9, Tables: 1, Pages: 16
                Funding
                The authors acknowledge the financial support of the funding agencies including Alberta Livestock and Meat Agency Ltd. (ALMA), Alberta Milk, and Natural Sciences and Engineering Research Council of Canada (NSERC) for this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                "All data are included within the manuscript." [No Supporting Information files exist for this ms.]

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