FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PLoS One / Lipidomic analysis of immune activation in equine leptospiro...
PloS one2018; 13(2); e0193424; doi: 10.1371/journal.pone.0193424

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses.

Abstract: Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.
Get Full Text
Publication Date: 2018-02-23 PubMed ID: 29474474PubMed Central: PMC5825116DOI: 10.1371/journal.pone.0193424Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study focuses on understanding the differences in the serum lipid profiles of horses naturally infected with Leptospira spp. compared to horses vaccinated against it. Techniques in lipidomic analysis were used and several lipid types, including cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens, were found increased in both infected and vaccinated horses.

Objective and Motivation

  • The research seeks to improve current diagnostic methods for leptospirosis, a bacterial disease, in horses. Present diagnostic methods cannot distinguish between antibodies produced due to vaccination and those resulting from natural infection.
  • The researchers aimed to investigate if there are any distinctive patterns in the lipid profile of horses naturally infected with Leptospira spp., a pathogen causing leptospirosis, and horses vaccinated against it.

Methodology

  • The research used a lipidomics approach, which is the large-scale study of pathways and networks of cellular lipids in biological systems. It applied a high-resolution mass spectrometry serum lipidomics analytical platform to discern differences in the serum lipid profiles.
  • Lipidomics can provide a comprehensive view of the cellular lipid metabolic processes and the changes associated with pathological states. In this case, it was used to identify lipid biomarkers unique to infection and vaccination against leptospirosis.

Results

  • The study identified that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens were elevated in the serum of both naturally infected and vaccinated horses.
  • The research found other lipids of interest: triacylglycerols levels were elevated only in the serum of naturally infected horses, while sphingomyelins increased only in the serum of vaccinated horses. This suggests their potential as more precise biomarkers for diagnostic differentiation.

Significance

  • This study represents the first exploration of equine serum lipidome during leptospiral infection and vaccination, providing precious insights into the lipid metabolic changes associated with both conditions.
  • The findings may lead to the development of improved diagnostic techniques that can accurately differentiate between natural infection and post-vaccination serum antibody responses in horses affected by leptospirosis.

Cite This Article

APA
Wood PL, Steinman M, Erol E, Carter C, Christmann U, Verma A. (2018). Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses. PLoS One, 13(2), e0193424. https://doi.org/10.1371/journal.pone.0193424

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 2
Pages: e0193424

Researcher Affiliations

Wood, Paul L
  • Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, Tennessee, United States of America.
Steinman, Margaret
  • Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, Kentucky, United States of America.
Erol, Erdal
  • Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, Kentucky, United States of America.
Carter, Craig
  • Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, Kentucky, United States of America.
Christmann, Undine
  • Center for Infectious, Zoonotic and Vector-borne Diseases, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, Tennessee, United States of America.
Verma, Ashutosh
  • Center for Infectious, Zoonotic and Vector-borne Diseases, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, Tennessee, United States of America.

MeSH Terms

  • Animals
  • Horse Diseases / immunology
  • Horse Diseases / metabolism
  • Horses
  • Leptospira / immunology
  • Leptospira / physiology
  • Leptospirosis / immunology
  • Leptospirosis / metabolism
  • Leptospirosis / veterinary
  • Lipid Metabolism
  • Vaccination

Conflict of Interest Statement

Competing Interests: All authors have no competing interests.

References

This article includes 53 references
  1. Adler B, de la Pena Moctezuma A. Leptospira and leptospirosis. Vet. Microbiol. 2010; 140:287–296.
    doi: 10.1016/j.vetmic.2009.03.012pubmed: 19345023google scholar: lookup
  2. Timoney J F, Kalimuthusamy N, Velineni S, Donahue J M, Artiushin S C, Fettinger M. A unique genotype of Leptospira interrogans serovar Pomona type kennewicki is associated with equine abortion. Vet Microbiol 2011; 150: 349–353.
    doi: 10.1016/j.vetmic.2011.02.049pubmed: 21450416google scholar: lookup
  3. Donahue J M, Smith B J, Poonacha K B, Donahoe J K, Rigsby C L. Prevalence and serovars of Leptospira involved in equine abortions in central Kentucky during the 1991–1993 foaling seasons. J. Vet. Diagn. Invest. 1995; 7:87–91.
    doi: 10.1177/104063879500700114pubmed: 7779971google scholar: lookup
  4. Verma A, Stevenson B, Adler B. Leptospirosis in horses. Veterinary Microbiology 2013; 167: 61–66.
    doi: 10.1016/j.vetmic.2013.04.012pubmed: 23647816google scholar: lookup
  5. Verma A, Stevenson B. Leptospiral uveitis- there is more to it than meets the eye!. Zoonoses Public Health 2012;59 (Suppl. 2) 132–141.
    pubmed: 22958257
  6. Carter C N, Cohen N, Steinman M N, Smith J L, Erol E, Brown S. Seroepidemiology of equine leptospirosis utilizing diagnostic laboratory specimens from 29 states (US) and one Canadian province. Proceedings of 55th Annual AAVLD Meet p51.
  7. Cole J R Jr, Sulzer C R, Pursell A R. Improved microtechnique for the leptospiral microscopic agglutination test. Appl Microbiol 1973; 25(6):976–980.
    pmc: PMC380950pubmed: 4736794
  8. Artushin S C, Timoney J F, Nally J, Verma A. Host-inducible immunogenic sphyngomyelinase-like protein, Lk73.5, of Leptospira interrogans. Infect. Immun. 2004; 72:742–749.
    doi: 10.1128/IAI.72.2.742-749.2004pmc: PMC321616pubmed: 14742516google scholar: lookup
  9. Verma A, Hellwage J, Artiushin S C, Zipfel P, Kraiczy P, Timoney J F. LfhA, a novel factor H binding protein of Leptospira interrogans. Infect. Immun. 2006; 74: 2659–2666.
    doi: 10.1128/IAI.74.5.2659-2666.2006pmc: PMC1459737pubmed: 16622202google scholar: lookup
  10. Palaniappan R U, Chang Y F, Jusuf S S, Artiushin S, Timoney J F, McDonough S P. Cloning and molecular characterization of an immunogenic LigA protein of Leptospira interrogans. Infect Immun 2002;70(11):5924–5930.
    doi: 10.1128/IAI.70.11.5924-5930.2002pmc: PMC130282pubmed: 12379666google scholar: lookup
  11. Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004; 45:1169–96.
    doi: 10.1194/jlr.R300019-JLR200pubmed: 15102878google scholar: lookup
  12. Grunfeld C, Feingold KR. Tumor necrosis factor, cytokines, and the hyperlipidemia of infection. Trends Endocrinol Metab 1991; 2:213–9.
    pubmed: 18411185
  13. Gazi IF, Apostolou FA, Liberopoulos EN, Filippatos TD, Tellis CC, Elisaf MS. Leptospirosis is associated with markedly increased triglycerides and small dense low-density lipoprotein and decreased high-density lipoprotein. Lipids 2011; 46:953–60.
    doi: 10.1007/s11745-011-3580-ypubmed: 21688175google scholar: lookup
  14. Liberopoulos EN, Apostolou F, Gazi IF, Kostara C, Bairaktari ET, Tselepis AD. Visceral leishmaniasis is associated with marked changes in serum lipid profile. Eur J Clin Invest 2014; 44:719–27.
    doi: 10.1111/eci.12288pubmed: 24920396google scholar: lookup
  15. Lamour SD, Gomez-Romero M, Vorkas PA, Alibu VP, Saric J, Holmes E. Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis. PLoS Negl Trop Dis 2015; 9:e0004200.
    doi: 10.1371/journal.pntd.0004200pmc: PMC4624234pubmed: 26505639google scholar: lookup
  16. Wood PL, Scoggin K, Ball BA, Troedsson MH, Squires EL. Lipidomics of equine sperm and seminal serum: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids. Theriogenology 2016; 86:1212–21.
    doi: 10.1016/j.theriogenology.2016.04.012pubmed: 27180330google scholar: lookup
  17. Wood PL, Barnette BL, Kaye JA, Quinn JF, Woltjer RL. Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer's disease subjects. Acta Neuropsychiatr 2015; 27:270–8.
    doi: 10.1017/neu.2015.18pubmed: 25858158google scholar: lookup
  18. Wood PL. Non-targeted lipidomics utilizing constant infusion high resolution ESI mass spectrometry In Springer Protocols, Neuromethods: Lipidomics. 2017; 125: 13–19.
  19. Vernel-Pauillac F, Merien F. Proinflammatory and immunomodulatory cytokine mRNA time course profiles in hamsters infected with a virulent variant of Leptospira interrogans. Infect Immun 2006; 74:4172–9.
    doi: 10.1128/IAI.00447-06pmc: PMC1489750pubmed: 16790792google scholar: lookup
  20. Naiman BM, Alt D, Bolin CA, Zuerner R, Baldwin CL. Protective killed Leptospira borgpetersenii vaccine induces potent Th1 immunity comprising responses by CD4 and gammadelta T lymphocytes. Infect Immun 2001; 69:7550–8.
    doi: 10.1128/IAI.69.12.7550-7558.2001pmc: PMC98846pubmed: 11705932google scholar: lookup
  21. Zuerner RL, Alt DP, Palmer MV, Thacker TC, Olsen SC. A Leptospira borgpetersenii serovar Hardjo vaccine induces a Th1 response, activates NK cells, and reduces renal colonization. Clin Vaccine Immunol 2011; 18:684–91.
    doi: 10.1128/CVI.00288-10pmc: PMC3122574pubmed: 21288995google scholar: lookup
  22. Tsukahara T, Tsukahara R, Fujiwara Y, Yue J, Cheng Y, Guo H. Phospholipase D2-dependent inhibition of the nuclear hormone receptor PPARgamma by cyclicphosphatidic acid. Mol Cell 2010; 39:421–32.
    doi: 10.1016/j.molcel.2010.07.022pmc: PMC3446787pubmed: 20705243google scholar: lookup
  23. Wood PL. Lipidomics of Alzheimer's disease: current status. Alzheimers Res Ther 2012; 4:5.
    doi: 10.1186/alzrt103pmc: PMC3471525pubmed: 22293144google scholar: lookup
  24. Losito I, Facchini L, Diomede S, Conte E, Megli FM, Cataldi TR. Hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry of a complex mixture of native and oxidized phospholipids. J Chromatogr A 2015; 1422:194–205.
    doi: 10.1016/j.chroma.2015.10.023pubmed: 26508677google scholar: lookup
  25. Nakagawa K, Kato S, Miyazawa T. Determination of Phosphatidylcholine Hydroperoxide (PCOOH) as a Marker of Membrane Lipid Peroxidation. J Nutr Sci Vitaminol (Tokyo) 2015; 61 Suppl:S78–80.
    doi: 10.3177/jnsv.61.S78pubmed: 26598897google scholar: lookup
  26. Schotthoefer AM, Schrodi SJ, Meece JK, Fritsche TR, Shukla SK. Pro-inflammatory immune responses are associated with clinical signs and symptoms of human anaplasmosis. PLoS One 2017; 12:e0179655.
    doi: 10.1371/journal.pone.0179655pmc: PMC5476275pubmed: 28628633google scholar: lookup
  27. Khovidhunkit W, Memon RA, Feingold KR, Grunfeld C. Infection and inflammation-induced proatherogenic changes of lipoproteins. J Infect Dis 2000; 181 Suppl 3:S462–72.
    doi: 10.1086/315611pubmed: 10839741google scholar: lookup
  28. Avelino-Silva VI, Miyaji KT, Hunt PW, Huang Y, Simoes M. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients. PLoS Negl Trop Dis 2016; 10:e0005219.
    doi: 10.1371/journal.pntd.0005219pmc: PMC5179051pubmed: 27941965google scholar: lookup
  29. Gomes STM, Gomes ÉR, Dos Santos MB, Lima SS, Queiroz MAF, Machado LFA. Immunological and virological characterization of HIV-1 viremia controllers in the North Region of Brazil. BMC Infect Dis 2017; 17:381.
    doi: 10.1186/s12879-017-2491-9pmc: PMC5455094pubmed: 28571570google scholar: lookup
  30. Cortés A, Muñoz-Antoli C, Esteban JG, Toledo R. Th2 and Th1 Responses: Clear and Hidden Sides of Immunity Against Intestinal Helminths. Trends Parasitol 2017.
    doi: 10.1016/j.pt.2017.05.004pubmed: 28566191google scholar: lookup
  31. Vitenberga Z, Pilmane M. Inflammatory, anti-inflammatory and regulatory cytokines in relatively healthy lung tissue as an essential part of the local immune system. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017; 161:164–173.
    doi: 10.5507/bp.2017.029pubmed: 28627525google scholar: lookup
  32. Wood PL. Roles of CNS macrophages in neurodegeneration In Neuroinflammation: Mechanisms and Management. pg 1–59.
  33. Nemeth ZH, Bogdanovski DA, Barratt-Stopper P, Paglinco SR, Antonioli L, Rolandelli RH. Crohn's Disease and Ulcerative Colitis Show Unique Cytokine Profiles. Cureus 2017; 9:e1177.
    doi: 10.7759/cureus.1177pmc: PMC5438231pubmed: 28533995google scholar: lookup
  34. Ait-Belkacem R, Bol V, Hamm G, Schramme F, Van Den Eynde B, Poncelet L. Microenvironment Tumor Metabolic Interactions Highlighted by qMSI: Application to the Tryptophan-Kynurenine Pathway in Immuno-Oncology. SLAS Discov 2017.
    doi: 10.1177/2472555217712659pubmed: 28557618google scholar: lookup
  35. Braidy N, Grant R. Kynurenine pathway metabolism and neuroinflammatory disease. Neural Regen Res 2017; 12:39–42.
    doi: 10.4103/1673-5374.198971pmc: PMC5319230pubmed: 28250737google scholar: lookup
  36. Wood PL. Differential regulation of IL-1 alpha and TNF alpha release from immortalized murine microglia (BV-2). Life Sci 1994; 55:661–8.
    pubmed: 8065228
  37. To KK, Lee KC, Wong SS, Sze KH, Ke YH, Lui YM. Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia. Diagn Microbiol Infect Dis 2016; 85:249–54.
    doi: 10.1016/j.diagmicrobio.2016.03.012pmc: PMC7173326pubmed: 27105773google scholar: lookup
  38. Scarpelini B, Zanoni M, Sucupira MC, Truong HM, Janini LM, Segurado ID. Serum Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment. PLoS One 2016; 11:e0161920.
    doi: 10.1371/journal.pone.0161920pmc: PMC5152829pubmed: 27941971google scholar: lookup
  39. Levett PN. Leptospirosis. Clin. Microbiol. Rev. 2001; 14:296–326.
    doi: 10.1128/CMR.14.2.296-326.2001pmc: PMC88975pubmed: 11292640google scholar: lookup
  40. Velineni S, Timoney JF. Preliminary evaluation of a dual antigen ELISA to distinguish vaccinated from Leptospira infected horses. Vet Rec 2016; 179:574.
    doi: 10.1136/vr.103686pubmed: 27650465google scholar: lookup
  41. Spiri AM, Rodriguez-Campos S, Matos JM, Glaus TM, Riond B, Reusch CE. Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine. BMC Vet Res 2017; 13:138.
    doi: 10.1186/s12917-017-1056-xpmc: PMC5445508pubmed: 28545521google scholar: lookup
  42. Christmann U, Buechner-Maxwell V, Witonsky S, Hite D, Wood PL. Levels of cyclic phosphatidic acid are increased in surfactant from asthmatic horses exposed to hay. 34th Annual Symposium of the Veterinary Comparative Respiratory Society, Lansing, Michigan, September 18-21st, 2016 .
  43. Jeewandara C, Gomes L, Udari S, Paranavitane SA, Shyamali NL, Ogg GS. Secretory phospholipase A2 in the pathogenesis of acute dengue infection. Immun Inflamm Dis 2016; 5:7–15.
    doi: 10.1002/iid3.135pmc: PMC5322161pubmed: 28250920google scholar: lookup
  44. Vijay R, Hua X, Meyerholz DK, Miki Y, Yamamoto K, Gelb M. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection. J Exp Med 2015; 212:1851–68.
    doi: 10.1084/jem.20150632pmc: PMC4612096pubmed: 26392224google scholar: lookup
  45. Brown HA, Thomas PG, Lindsley CW. Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nat Rev Drug Discov 2017; 16:351–367.
    doi: 10.1038/nrd.2016.252pmc: PMC6040825pubmed: 28209987google scholar: lookup
  46. Lucas EA, Billington SJ, Carlson P, McGee DJ, Jost BH. Phospholipase D promotes Arcanobacterium haemolyticum adhesion via lipid raft remodeling and host cell death following bacterial invasion. BMC Microbiol 2010; 10:270.
    doi: 10.1186/1471-2180-10-270pmc: PMC2978216pubmed: 20973961google scholar: lookup
  47. Fujiwara Y. Cyclic phosphatidic acid—a unique bioactive phospholipid. Biochim Biophys Acta 2008; 1781:519–24.
    doi: 10.1016/j.bbalip.2008.05.002pmc: PMC2572151pubmed: 18554524google scholar: lookup
  48. Tsukahara T. PPAR γ Networks in Cell Signaling: Update and Impact of Cyclic Phosphatidic Acid. J Lipids 2013; 2013:246597.
    doi: 10.1155/2013/246597pmc: PMC3582055pubmed: 23476786google scholar: lookup
  49. Tsukahara T, Haniu H, Matsuda Y. Cyclic phosphatidic acid inhibits alkyl-glycerophosphate-induced downregulation of histone deacetylase 2 expression and suppresses the inflammatory response in human coronary artery endothelial cells. Int J Med Sci 2014; 11:955–61.
    doi: 10.7150/ijms.9316pmc: PMC4081316pubmed: 25013374google scholar: lookup
  50. Gotoh M, Nagano A, Tsukahara R, Murofushi H, Morohoshi T, Otsuka K. Cyclic phosphatidic acid relieves osteoarthritis symptoms. Mol Pain 2014;10:52.
    doi: 10.1186/1744-8069-10-52pmc: PMC4141741pubmed: 25123228google scholar: lookup
  51. Yamamoto S, Gotoh M, Kawamura Y, Yamashina K, Yagishita S, Awaji T. Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice. Eur J Pharmacol 2014; 741:17–24.
    doi: 10.1016/j.ejphar.2014.07.040pubmed: 25084219google scholar: lookup
  52. Tsukahara T, Matsuda Y, Haniu H. Cyclic phosphatidic acid stimulates cAMP production and inhibits growth in human colon cancer cells. PLoS One 2013; 8:e81139.
    doi: 10.1371/journal.pone.0081139pmc: PMC3839875pubmed: 24282571google scholar: lookup
  53. Lau SK, Lee KC, Lo GC, Ding VS, Chow WN, Ke TY. Metabolomic Profiling of Serum from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis. Int J Mol Sci 2016; 17:307.
    doi: 10.3390/ijms17030307pmc: PMC4813170pubmed: 26927094google scholar: lookup

Citations

This article has been cited 7 times.
  1. Mönki J, Mykkänen A. Lipids in Equine Airway Inflammation: An Overview of Current Knowledge. Animals (Basel) 2024 Jun 18;14(12).
    doi: 10.3390/ani14121812pubmed: 38929431google scholar: lookup
  2. Mönki J, Holopainen M, Ruhanen H, Karikoski N, Käkelä R, Mykkänen A. Lipid species profiling of bronchoalveolar lavage fluid cells of horses housed on two different bedding materials. Sci Rep 2023 Dec 8;13(1):21778.
    doi: 10.1038/s41598-023-49032-1pubmed: 38066223google scholar: lookup
  3. Ramin A, Abdollahpour G, Hosseinzadeh A, Azizzadeh F, Ramin P, Klalili Y, Sanajo D, Iran Nezhad S. Comparison of anti-Leptospira antibodies by microscopic agglutination test in ruminants and equines of Urmia, Iran. Vet Res Forum 2023;14(4):229-235.
    doi: 10.30466/vrf.2022.546475.3345pubmed: 37181853google scholar: lookup
  4. Wood PL, Muir W, Christmann U, Gibbons P, Hancock CL, Poole CM, Emery AL, Poovey JR, Hagg C, Scarborough JH, Christopher JS, Dixon AT, Craney DJ. Lipidomics of the chicken egg yolk: high-resolution mass spectrometric characterization of nutritional lipid families. Poult Sci 2021 Feb;100(2):887-899.
    doi: 10.1016/j.psj.2020.11.020pubmed: 33518142google scholar: lookup
  5. Shibaike Y, Gotoh M, Ogawa C, Nakajima S, Yoshikawa K, Kobayashi T, Murakami-Murofushi K. 2-Carba cyclic phosphatidic acid inhibits lipopolysaccharide-induced prostaglandin E2 production in a human macrophage cell line. Biochem Biophys Rep 2019 Sep;19:100668.
    doi: 10.1016/j.bbrep.2019.100668pubmed: 31367683google scholar: lookup
  6. Wood PL, Donohue MN, Cebak JE, Beckmann TG, Treece M, Johnson JW, Miller LMJ. Tear Film Amphiphilic and Anti-Inflammatory Lipids in Bovine Pink Eye. Metabolites 2018 Nov 21;8(4).
    doi: 10.3390/metabo8040081pubmed: 30469369google scholar: lookup
  7. Raeven RHM, van Riet E, Meiring HD, Metz B, Kersten GFA. Systems vaccinology and big data in the vaccine development chain. Immunology 2019 Jan;156(1):33-46.
    doi: 10.1111/imm.13012pubmed: 30317555google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.