Abstract
Footrot (FR) is a common, contagious bacterial disease of sheep that results in lameness and significant economic losses for producers. We previously reported that sheep affected with FR have lower whole-blood (WB) selenium (Se) concentrations and that Se supplementation in conjunction with routine control practices accelerates recovery from FR. To determine whether oral Se-yeast administered at supranutritional levels (>4.9 mg Se/week) alters the ability of sheep to resist or recover from FR infection, 60 ewes with and 60 ewes without FR were drenched once weekly for 62.5 weeks with 0, 4.9, 14.7, or 24.5 mg organic Se-yeast (30 ewes per treatment group). Footrot prevalence and severity were measured at 0, 20, 28, 40, and 60 weeks of Se supplementation. Genomic expression of eight WB-neutrophil genes for selenoproteins and seven WB-neutrophil genes for proteins involved in innate immunity was determined at the end of the treatment period using SYBR Green and quantitative polymerase chain reaction methodology. Supranutritional Se-yeast supplementation successfully increased Se status in sheep but did not prevent FR. Supranutritional Se-yeast supplementation increased WB-neutrophil expression of genes involved in innate immunity: l-selectin, interleukin-8 receptor, and toll-like receptor 4, which were or tended to be lower in ewes affected with FR. Furthermore, supranutritional Se-yeast supplementation altered the expression of selenoprotein genes involved in innate immunity, increasing selenoprotein S and glutathione peroxidase 4 and decreasing iodothyronine deiodinases 2 and 3. In conclusion, supranutritional Se-yeast supplementation does not prevent FR, but does alter WB-neutrophil gene expression profiles associated with innate immunity, including reversing those impacted by FR.
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Abbreviations
- COX II:
-
Cyclooxygenase II
- Dio:
-
Iodothyronine deiodinases
- FBS:
-
Fetal bovine serum
- FOS:
-
FBJ murine osteosarcoma viral oncogene homolog or c-FOS, and a member of the activator protein-1 family
- FR:
-
Footrot
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GPx:
-
Glutathione peroxidases
- HBSS:
-
Hank's balanced saline solution
- ICP-MS:
-
Ionized coupled plasma mass spectrometry
- IFN-γ:
-
Interferon-gamma
- IL-8R:
-
Interleukin-8 receptor
- l-Sel:
-
l-Selectin
- NFκB:
-
Nuclear factor kappa B
- PBS:
-
Phosphate buffered saline
- PPM1A:
-
Protein phosphatase magnesium-dependent 1A
- qPCR:
-
Quantitative polymerase chain reaction
- RBC:
-
Red blood cells
- ROS:
-
Reactive oxygen species
- RPL19:
-
Ribosomal protein large subunit family member-19
- Se:
-
Selenium
- SeCys:
-
Selenocysteine
- SeMet:
-
Selenomethionine
- SEP:
-
Selenoproteins
- TBK1:
-
TANK-binding kinase 1
- TLR4:
-
Toll-like receptor 4
- TxnR:
-
Thioredoxin reductase
- WB:
-
Whole blood
References
NRC (2005) Mineral tolerance of animals, 2nd edn. National Academy Press, Washington, DC
Hoffmann PR, Berry MJ (2008) The influence of selenium on immune responses. Mol Nutr Food Res 52(11):1273–1280. doi:10.1002/mnfr.200700330
Rayman MP (2012) Selenium and human health. Lancet 379(9822):1256–1268. doi:10.1016/S0140-6736(11)61452-9
Bellinger FP, Raman AV, Reeves MA, Berry MJ (2009) Regulation and function of selenoproteins in human disease. Biochem J 422(1):11–22. doi:10.1042/BJ20090219
Ferguson LR, Karunasinghe N, Zhu S, Wang AH (2012) Selenium and its' role in the maintenance of genomic stability. Mutat Res 733(1–2):100–110. doi:10.1016/j.mrfmmm.2011.12.011
Brigelius-Flohe R (2006) Glutathione peroxidases and redox-regulated transcription factors. Biol Chem 387(10–11):1329–1335. doi:10.1515/BC.2006.166
Saito Y, Hayashi T, Tanaka A, Watanabe Y, Suzuki M, Saito E, Takahashi K (1999) Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p. J Biol Chem 274(5):2866–2871
Whanger PD (2000) Selenoprotein W: a review. Cell Mol Life Sci 57(13–14):1846–1852
Rooke JA, Robinson JJ, Arthur JR (2004) Effects of vitamin E and selenium on the performance and immune status of ewes and lambs. J Agr Sci 142:253–262. doi:10.1017/S0021859604004368
Kim KH, Gao Y, Walder K, Collier GR, Skelton J, Kissebah AH (2007) SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis. Biochem Biophys Res Commun 354(1):127–132. doi:10.1016/j.bbrc.2006.12.183
Curran JE, Jowett JB, Elliott KS, Gao Y, Gluschenko K, Wang J, Abel Azim DM, Cai G, Mahaney MC, Comuzzie AG, Dyer TD, Walder KR, Zimmet P, MacCluer JW, Collier GR, Kissebah AH, Blangero J (2005) Genetic variation in selenoprotein S influences inflammatory response. Nat Genet 37(11):1234–1241. doi:10.1038/ng1655
Cheng AWM, Bolognesi M, Kraus VB (2012) DIO2 modifies inflammatory responses in chondrocytes. Osteoarthr Cartilage 20(5):440–445. doi:10.1016/j.joca.2012.02.006
Kiremidjian-Schumacher L, Stotzky G (1987) Selenium and immune responses. Environ Res 42(2):277–303
Finch JM, Turner RJ (1996) Effects of selenium and vitamin E on the immune responses of domestic animals. Res Vet Sci 60(2):97–106
McClure SJ (2008) How minerals may influence the development and expression of immunity to endoparasites in livestock. Parasite Immunol 30(2):89–100. doi:10.1111/j.1365-3024.2007.00996.x
Hefnawy AE, Tortora-Perez JL (2010) The importance of selenium and the effects of its deficiency in animal health. Small Ruminant Res 89(2–3):185–192. doi:10.1016/j.smallrumres.2009.12.042
Swecker WS, Eversole DE, Thatcher CD, Blodgett DJ, Schurig GG, Meldrum JB (1989) Influence of supplemental selenium on humoral immune-responses in weaned beef-calves. Am J Vet Res 50(10):1760–1763
FDA (2012) Code of federal regulations title 21—food and drugs chapter 1—Food and Drug Administration, Department of Health and Human Services Subchapter E—animal drugs, feeds, and related products Part 573—Food additive permitted in feed and drinking water of animals Subpart B—Food Additive Listing Section 573920—Selenium
Fairweather-Tait SJ, Collings R, Hurst R (2010) Selenium bioavailability: current knowledge and future research requirements. Am J Clin Nutr 91(5):1484S–1491S. doi:10.3945/ajcn.2010.28674J
Zeng H, Combs GF Jr (2008) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 19(1):1–7. doi:10.1016/j.jnutbio.2007.02.005
Hall JA, Harwell AM, Van Saun RJ, Vorachek WR, Stewart WC, Galbraith ML, Hooper KJ, Hunter JK, Mosher WD, Pirelli GJ (2011) Agronomic biofortification with selenium: effects on whole blood selenium and humoral immunity in beef cattle. Anim Feed Sci Tech 164(3–4):184–190. doi:10.1016/j.anifeedsci.2011.01.009
Stewart WC, Bobe G, Pirelli GJ, Mosher WD, Hall JA (2012) Organic and inorganic selenium: III. Ewe and progeny performance J Anim Sci 90(12):4536–4543. doi:10.2527/jas.2011-5019
Stewart WC, Bobe G, Vorachek WR, Stang BV, Pirelli GJ, Mosher WD, Hall JA (2013) Organic and inorganic selenium: IV. Passive transfer of immunoglobulin from ewe to lamb. J Anim Sci 91(4):1791–1800. doi:10.2527/jas.2012-5377
Marshall DJ, Walker RI, Cullis BR, Luff MF (1991) The effect of footrot on body weight and wool growth of sheep. Aust Vet J 68(2):45–49
Kennan RM, Han X, Porter CJ, Rood JI (2011) The pathogenesis of ovine footrot. Vet Microbiol 153(1–2):59–66. doi:10.1016/j.vetmic.2011.04.005
Bennett GN, Hickford JG (2011) Ovine footrot: new approaches to an old disease. Vet Microbiol 148(1):1–7. doi:10.1016/j.vetmic.2010.09.003
Hall JA, Sendek RL, Chinn RM, Bailey DP, Thonstad KN, Wang Y, Forsberg NE, Vorachek WR, Stang BV, Van Saun RJ, Bobe G (2011) Higher whole-blood selenium is associated with improved immune responses in footrot-affected sheep. Vet Res 42(1):99. doi:10.1186/1297-9716-42-99
Hall JA, Van Saun RJ, Bobe G, Stewart WC, Vorachek WR, Mosher WD, Nichols T, Forsberg NE, Pirelli GJ (2012) Organic and inorganic selenium: I Oral bioavailability in ewes. J Anim Sci 90(2):568–576. doi:10.2527/jas.2011-4075
NRC (2007) Nutrient requirements of small ruminants: sheep, goats, cervids, and new world camelids. National Academy Press, Washington, DC
Bulgin MS, Lincoln SD, Lane VM, South PJ, Dahmen JJ, Gradin JL, Smith AW (1985) Evaluating an ovine foot-rot vaccine. Vet Med-Us 80(2):105–113
Winter AC (2009) Footrot control and eradication (elimination) strategies. Small Ruminant Res 86(1–3):90–93. doi:10.1016/j.smallrumres.2009.09.026
Wang Y, Puntenney SB, Burton JL, Forsberg NE (2007) Ability of a commercial feed additive to modulate expression of innate immunity in sheep immunosuppressed with dexamethasone. Animal 1(7):945–951. doi:10.1017/S1751731107000365
Green LE, George TR (2008) Assessment of current knowledge of footrot in sheep with particular reference to Dichelobacter nodosus and implications for elimination or control strategies for sheep in Great Britain. Vet J 175(2):173–180. doi:10.1016/j.tvjl.2007.01.014
Hall JA, Bailey DP, Thonstad KN, Van Saun RJ (2009) Effect of parenteral selenium administration to sheep on prevalence and recovery from footrot. J Vet Intern Med 23(2):352–358. doi:10.1111/j.1939-1676.2008.0253.x
Whanger PD (2002) Selenocompounds in plants and animals and their biological significance. J Am Coll Nutr 21(3):223–232
Rayman MP (2008) Food-chain selenium and human health: emphasis on intake. Br J Nutr 100(2):254–268. doi:10.1017/S0007114508939830
Deagen JT, Butler JA, Zachara BA, Whanger PD (1993) Determination of the distribution of selenium between glutathione peroxidase, selenoprotein P, and albumin in plasma. Anal Biochem 208(1):176–181. doi:10.1006/abio.1993.1025
Finley JW (1998) The absorption and tissue distribution of selenium from high-selenium broccoli are different from selenium from sodium selenite, sodium selenate, and selenomethionine as determined in selenium-deficient rats. J Agr Food Chem 46(9):3702–3707. doi:10.1021/Jf980027q
Whanger P, Vendeland S, Park YC, Xia YM (1996) Metabolism of subtoxic levels of selenium in animals and humans. Ann Clin Lab Sci 26(2):99–113
Woolaston RR (1993) Factors affecting the prevalence and severity of footrot in a Merino flock selected for resistance to Haemonchus contortus. Aust Vet J 70(10):365–369. doi:10.1111/j.1751-0813.1993.tb00809.x
Sammalkorpi K, Valtonen V, Alfthan G, Aro A, Huttunen J (1988) Serum selenium in acute infections. Infection 16(4):222–224. doi:10.1007/Bf01650756
Cederlof SE, Hansen T, Klaas IC, Angen O (2013) An evaluation of the ability of Dichelobacter nodosus to survive in soil. Acta Vet Scand 55:4. doi:10.1186/1751-0147-55-4
Kaler J, Daniels SL, Wright JL, Green LE (2010) Randomized clinical trial of long-acting oxytetracycline, foot trimming, and flunixine meglumine on time to recovery in sheep with footrot. J Vet Intern Med 24(2):420–425. doi:10.1111/j.1939-1676.2009.0450.x
Waddell TK, Fialkow L, Chan CK, Kishimoto TK, Downey GP (1995) Signaling functions of L-selectin. Enhancement of tyrosine phosphorylation and activation of MAP kinase. J Biol Chem 270(25):15403–15411
Mitchell GB, Albright BN, Caswell JL (2003) Effect of interleukin-8 and granulocyte colony-stimulating factor on priming and activation of bovine neutrophils. Infect Immun 71(4):1643–1649
Jozsef L, Khreiss T, El Kebir D, Filep JG (2006) Activation of TLR-9 induces IL-8 secretion through peroxynitrite signaling in human neutrophils. J Immunol 176(2):1195–1202
Kettritz R, Gaido ML, Haller H, Luft FC, Jennette CJ, Falk RJ (1998) Interleukin-8 delays spontaneous and tumor necrosis factor-alpha-mediated apoptosis of human neutrophils. Kidney Int 53(1):84–91. doi:10.1046/j.1523-1755.1998.00741.x
Ingvartsen KL, Moyes K (2013) Nutrition, immune function and health of dairy cattle. Animal 7(Suppl 1):112–122. doi:10.1017/S175173111200170X
Ndiweni N, Finch JM (1996) Effects of in vitro supplementation with alpha-tocopherol and selenium on bovine neutrophil functions: implications for resistance to mastitis. Vet Immunol Immunopathol 51(1–2):67–78
Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4(5):491–496. doi:10.1038/ni921
Hill CS (2006) Identification of a Smad phosphatase. ACS Chem Biol 1(6):346–348. doi:10.1021/cb6002702
Sunde RA, Raines AM, Barnes KM, Evenson JK (2009) Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome. Bioscience Rep 29(5):329–338. doi:10.1042/Bsr20080146
Carlson BA, Yoo MH, Tsuji PA, Gladyshev VN, Hatfield DL (2009) Mouse models targeting selenocysteine tRNA expression for elucidating the role of selenoproteins in health and development. Molecules 14(9):3509–3527. doi:10.3390/molecules14093509
Barnes KM, Evenson JK, Raines AM, Sunde RA (2009) Transcript analysis of the selenoproteome indicates that dietary selenium requirements of rats based on selenium-regulated selenoprotein mRNA levels are uniformly less than those based on glutathione peroxidase activity. J Nutr 139(2):199–206. doi:10.3945/jn.108.098624
McCann JC, Ames BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. FASEB J 25(6):1793–1814. doi:10.1096/fj.11-180885
Brigelius-Flohe R, Kipp A (2009) Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta 1790(11):1555–1568. doi:10.1016/j.bbagen.2009.03.006
Heirman I, Ginneberge D, Brigelius-Flohe R, Hendrickx N, Agostinis P, Brouckaert P, Rottiers P, Grooten J (2006) Blocking tumor cell eicosanoid synthesis by GP x 4 impedes tumor growth and malignancy. Free Radic Biol Med 40(2):285–294. doi:10.1016/j.freeradbiomed.2005.08.033
Goldson AJ, Fairweather-Tait SJ, Armah CN, Bao Y, Broadley MR, Dainty JR, Furniss C, Hart DJ, Teucher B, Hurst R (2011) Effects of selenium supplementation on selenoprotein gene expression and response to influenza vaccine challenge: a randomised controlled trial. PLoS One 6(3):e14771. doi:10.1371/journal.pone.0014771
Boelen A, Kwakkel J, Alkemade A, Renckens R, Kaptein E, Kuiper G, Wiersinga WM, Visser TJ (2005) Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation. Endocrinology 146(12):5128–5134. doi:10.1210/en.2005-0608
Boelen A, Boorsma J, Kwakkel J, Wieland CW, Renckens R, Visser TJ, Fliers E, Wiersinga WM (2008) Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection. Thyroid 18(10):1095–1103. doi:10.1089/thy.2008.0090
Boelen A, Mikita J, Boiziau C, Chassande O, Fliers E, Petry KG (2009) Type 3 deiodinase expression in inflammatory spinal cord lesions in rat experimental autoimmune encephalomyelitis. Thyroid 19(12):1401–1406. doi:10.1089/thy.2009.0228
Ma SF, Xie L, Pino-Yanes M, Sammani S, Wade MS, Letsiou E, Siegler J, Wang T, Infusino G, Kittles RA, Flores C, Zhou T, Prabhakar BS, Moreno-Vinasco L, Villar J, Jacobson JR, Dudek SM, Garcia JG (2011) Type 2 deiodinase and host responses of sepsis and acute lung injury. Am J Respir Cell Mol Biol 45(6):1203–1211. doi:10.1165/rcmb.2011-0179OC
Felix K, Gerstmeier S, Kyriakopoulos A, Howard OM, Dong HF, Eckhaus M, Behne D, Bornkamm GW, Janz S (2004) Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice. Cancer Res 64(8):2910–2917
Novoselov SV, Calvisi DF, Labunskyy VM, Factor VM, Carlson BA, Fomenko DE, Moustafa ME, Hatfield DL, Gladyshev VN (2005) Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice. Oncogene 24(54):8003–8011. doi:10.1038/sj.onc.1208940
Moustafa ME, Carlson BA, Anver MR, Bobe G, Zhong N, Ward JM, Perella CM, Hoffmann VJ, Rogers K, Combs GF Jr, Schweizer U, Merlino G, Gladyshev VN, Hatfield DL (2013) Selenium and selenoprotein deficiencies induce widespread pyogranuloma formation in mice, while high levels of dietary selenium decrease liver tumor size driven by TGFalpha. PLoS One 8(2):e57389. doi:10.1371/journal.pone.0057389
Diwadkar-Navsariwala V, Prins GS, Swanson SM, Birch LA, Ray VH, Hedayat S, Lantvit DL, Diamond AM (2006) Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model. Proc Natl Acad Sci U S A 103(21):8179–8184. doi:10.1073/pnas.0508218103
Irons R, Carlson BA, Hatfield DL, Davis CD (2006) Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression. J Nutr 136(5):1311–1317
Hudson TS, Carlson BA, Hoeneroff MJ, Young HA, Sordillo L, Muller WJ, Hatfield DL, Green JE (2012) Selenoproteins reduce susceptibility to DMBA-induced mammary carcinogenesis. Carcinogenesis 33(6):1225–1230. doi:10.1093/carcin/bgs129
Walston J, Xue Q, Semba RD, Ferrucci L, Cappola AR, Ricks M, Guralnik J, Fried LP (2006) Serum antioxidants, inflammation, and total mortality in older women. Am J Epidemiol 163(1):18–26. doi:10.1093/aje/kwj007
Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270. doi:10.1146/annurev.med.51.1.245
Hall JA, Chinn RM, Vorachek WR, Gorman ME, Jewell DE (2010) Aged Beagle dogs have decreased neutrophil phagocytosis and neutrophil-related gene expression compared to younger dogs. Vet Immunol Immunopathol 137(1–2):130–135. doi:10.1016/j.vetimm.2010.05.002
Garcia-Crespo D, Juste RA, Hurtado A (2005) Selection of ovine housekeeping genes for normalisation by real-time RT-PCR; analysis of PrP gene expression and genetic susceptibility to scrapie. BMC Vet Res 1:3. doi:10.1186/1746-6148-1-3
O'Gorman GM, Park SD, Hill EW, Meade KG, Coussens PM, Agaba M, Naessens J, Kemp SJ, MacHugh DE (2009) Transcriptional profiling of cattle infected with Trypanosoma congolense highlights gene expression signatures underlying trypanotolerance and trypanosusceptibility. BMC Genomics 10:207. doi:10.1186/1471-2164-10-207
Connor EE, Laiakis EC, Fernandes VM, Williams JL, Capuco AV (2005) Molecular cloning, expression and radiation hybrid mapping of the bovine deiodinase type II (DIO2) and deiodinase type III (DIO3) genes. Anim Genet 36(3):240–243. doi:10.1111/j.1365-2052.2005.01282.x
Lum GE, Rowntree JE, Bondioli KR, Southern LL, Williams CC (2009) The influence of dietary selenium on common indicators of selenium status and liver glutathione peroxidase-1 messenger ribonucleic acid. J Anim Sci 87(5):1739–1746. doi:10.2527/jas.2008-1417
Brennan KM, Terry EN, Michal JJ, Kincaid RL, Johnson KA (2009) Body weight loss in beef cows: II. Increased antioxidant messenger ribonucleic acid levels in skeletal muscle but not erythrocyte antioxidant activity. J Anim Sci 87(9):2867–2873. doi:10.2527/jas.2008-1301
Bhide MR, Mucha R, Mikula I Jr, Kisova L, Skrabana R, Novak M, Mikula I Sr (2009) Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection. BMC Genet. doi:10.1186/1471-2156-10-21
Meade KG, Gormley E, Doyle MB, Fitzsimons T, O'Farrelly C, Costello E, Keane J, Zhao Y, MacHugh DE (2007) Innate gene repression associated with Mycobacterium bovis infection in cattle: toward a gene signature of disease. BMC Genomics 8:400. doi:10.1186/1471-2164-8-400
Tajima S, Aida Y (2002) Mutant tax protein from bovine leukemia virus with enhanced ability to activate the expression of c-fos. J Virol 76(5):2557–2562
Stewart WC, Bobe G, Vorachek WR, Pirelli GJ, Mosher WD, Nichols T, Van Saun RJ, Forsberg NE, Hall JA (2012) Organic and inorganic selenium: II. Transfer efficiency from ewes to lambs. J Anim Sci 90(2):577–584. doi:10.2527/jas.2011-4076
Acknowledgments
The authors thank Thomas Nichols, Sheep Center Director, Department of Animal and Rangeland Sciences, College of Agricultural Sciences, Oregon State University, for hoof examination, trimming, and foot scoring for FR. This study was funded in part by USDA CSREES 2008-35204-04624, Agricultural Research Foundation, and Animal Health and Disease Project Formula Funds, Oregon State University, Corvallis, OR.
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Hugejiletu, H., Bobe, G., Vorachek, W.R. et al. Selenium Supplementation Alters Gene Expression Profiles Associated with Innate Immunity in Whole-Blood Neutrophils of Sheep. Biol Trace Elem Res 154, 28–44 (2013). https://doi.org/10.1007/s12011-013-9716-6
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DOI: https://doi.org/10.1007/s12011-013-9716-6