Skip to main content
SpringerLink
Log in

Exploration of Serum Marker Proteins in Mice Induced by Babesia microti Infection Using a Quantitative Proteomic Approach

  • Published:
The Protein Journal Aims and scope Submit manuscript

Abstract

Babesia microti is a protozoan that mainly parasitizes rodent and human erythrocytes. B. microti infection can result in changes in the expression levels of various proteins in the host serum. To explore the mechanism underlying the regulation of serum proteins by the host during B. microti infection, this study used a data-independent acquisition (DIA) quantitative proteomic approach to perform comprehensive quantitative proteomic analysis on the serum of B. microti-infected mice. We identified and analysed 333 serum proteins during the infectious stage and recovery stage within 30 days of infection by B. microti in mice. Through quantitative analysis, we found 57 proteins differentially expressed in the infection stage and 69 proteins differentially expressed in the recovery stage. Bioinformatics analysis revealed that these differentially expressed proteins were mainly concentrated in organelles, cell parts, and extracellular regions that are mainly involved in immune system, metabolic, and cellular processes. Additionally, the differentially expressed proteins mainly had catalytic activity. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis showed that many of the differentially expressed proteins participate in the complement and coagulation cascade reaction, including complement C3, complement FP, and coagulation factor XII. The results of this study can provide more information for the selection of biomarkers for the early clinical monitoring of babesiosis and help in the treatment of babesiosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Lobo CA, Cursino-Santos JR, Alhassan A, Rodrigues M (2013) Babesia: an emerging infectious threat in transfusion medicine. PLoS Pathog 9:e1003387. https://doi.org/10.1371/journal.ppat.1003387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vannier EG, Diuk-Wasser MA, Ben Mamoun C, Krause PJ (2015) Babesiosis. Infect Dis Clin North Am 29:357–370. https://doi.org/10.1016/j.idc.2015.02.008

    Article  PubMed  PubMed Central  Google Scholar 

  3. Vannier E, Krause PJ (2012) Human babesiosis. N Engl J Med 366:2397–2407. https://doi.org/10.1056/NEJMra1202018

    Article  CAS  PubMed  Google Scholar 

  4. Kules J, Mrljak V, Baric Rafaj R, Selanec J, Burchmore R, Eckersall PD (2014) Identification of serum biomarkers in dogs naturally infected with Babesia canis canis using a proteomic approach. BMC Vet Res 10:111. https://doi.org/10.1186/1746-6148-10-111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ray S, Srivastava R, Tripathi K, Vaibhav V, Patankar S, Srivastava S (2012) Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets? OMICS 16:527–536. https://doi.org/10.1089/omi.2012.0037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xu B, Liu XF, Cai YC, Huang JL, Zhang RX, Chen JH, Cheng XJ, Zhou X, Xu XN, Zhou Y, Zhang T, Chen SB, Li J, Wu QF, Sun CS, Fu YF, Chen JX, Zhou XN, Hu W (2018) Screening for biomarkers reflecting the progression of Babesia microti infection. Parasites Vectors 11:379. https://doi.org/10.1186/s13071-018-2951-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang M, Hu Y, Li M, Xu Q, Zhang X, Wang X, Xue X, Xiao Q, Liu J, Wang H (2020) A proteomics analysis of the ovarian development in females of Haemaphysalis longicornis. Exp Appl Acarol 80:289–309. https://doi.org/10.1007/s10493-020-00469-3

    Article  CAS  PubMed  Google Scholar 

  8. Ma J, Chen T, Wu SF, Yang CY, Bai MZ, Shu KX, Li KL, Zhang GQ, Jin Z, He FC, Hermjakob H, Zhu YP (2019) iProX: an integrated proteome resource. Nucleic Acids Res 47:D1211–D1217. https://doi.org/10.1093/nar/gky869

    Article  PubMed  Google Scholar 

  9. Jung JY, Kwak YH, Kim KS, Kwon WY, Suh GJ (2015) Change of hemopexin level is associated with the severity of sepsis in endotoxemic rat model and the outcome of septic patients. J Crit Care 30:525–530. https://doi.org/10.1016/j.jcrc.2014.12.009

    Article  CAS  PubMed  Google Scholar 

  10. Garland P, Durnford AJ, Okemefuna AI, Dunbar J, Nicoll JA, Galea J, Boche D, Bulters DO, Galea I (2016) Heme-hemopexin scavenging is active in the brain and associates with outcome after subarachnoid hemorrhage. Stroke 47:872–876. https://doi.org/10.1161/STROKEAHA.115.011956

    Article  CAS  PubMed  Google Scholar 

  11. Wei Q, Tsuji M, Zamoto A, Kohsaki M, Matsui T, Shiota T, Telford SR, Ishihara C (2001) Human babesiosis in Japan: isolation of Babesia microti-like parasites from an asymptomatic transfusion donor and from a rodent from an area where babesiosis is endemic. J Clin Microbiol 39:2178–2183. https://doi.org/10.1128/JCM.39.6.2178-2183.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Honey K, Rudensky AY (2003) Lysosomal cysteine proteases regulate antigen presentation. Nat Rev Immunol 3:472–482. https://doi.org/10.1038/nri1110

    Article  CAS  PubMed  Google Scholar 

  13. Aggarwal N, Sloane BF (2014) Cathepsin B: multiple roles in cancer. Proteomics Clin Appl 8:427–437. https://doi.org/10.1002/prca.201300105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Choi-Miura NH (2004) Novel human plasma proteins, IHRP (acute phase protein) and PHBP (serine protease), which bind to glycosaminoglycans. Curr Med Chem Cardiovasc Hematol Agents 2:239–248. https://doi.org/10.2174/1568016043356327

    Article  CAS  PubMed  Google Scholar 

  15. Zhuo L, Kimata K (2008) Structure and function of inter-alpha-trypsin inhibitor heavy chains. Connect Tissue Res 49:311–320. https://doi.org/10.1080/03008200802325458

    Article  CAS  PubMed  Google Scholar 

  16. Bajic G, Degn SE, Thiel S, Andersen GR (2015) Complement activation, regulation, and molecular basis for complement-related diseases. EMBO J 34:2735–2757. https://doi.org/10.15252/embj.201591881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Muller-Eberhard HJ (1985) The killer molecule of complement. J Investig Dermatol 85:47s–52s. https://doi.org/10.1111/1523-1747.ep12275445

    Article  CAS  PubMed  Google Scholar 

  18. Ursini F, Russo E, Mauro D, Abenavoli L, Ammerata G, Serrao A, Grembiale RD, De Sarro G, Olivieri I, D’Angelo S (2017) Complement C3 and fatty liver disease in rheumatoid arthritis patients: a cross-sectional study. Eur J Clin Investig 47:728–735. https://doi.org/10.1111/eci.12798

    Article  CAS  Google Scholar 

  19. Okla H, Jasik KP, Slodki J, Rozwadowska B, Slodki A, Jurzak M, Pierzchala E (2014) Hepatic tissue changes in rats due to chronic invasion of Babesia microti. Folia Biol (Krakow) 62:353–359. https://doi.org/10.3409/fb62_4.353

    Article  Google Scholar 

  20. Fearon DT, Austen KF (1975) Properdin: initiation of alternative complement pathway. Proc Natl Acad Sci USA 72:3220–3224. https://doi.org/10.1073/pnas.72.8.3220

    Article  CAS  PubMed  Google Scholar 

  21. Blatt AZ, Pathan S, Ferreira VP (2016) Properdin: a tightly regulated critical inflammatory modulator. Immunol Rev 274:172–190. https://doi.org/10.1111/imr.12466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD (2007) Complement and coagulation: strangers or partners in crime? Trends Immunol 28:184–192. https://doi.org/10.1016/j.it.2007.02.006

    Article  CAS  PubMed  Google Scholar 

  23. Ritis K, Doumas M, Mastellos D, Micheli A, Giaglis S, Magotti P, Rafail S, Kartalis G, Sideras P, Lambris JD (2006) A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. J Immunol 177:4794–4802. https://doi.org/10.4049/jimmunol.177.7.4794

    Article  CAS  PubMed  Google Scholar 

  24. Ueda Y, Miwa T, Gullipalli D, Sato S, Ito D, Kim H, Palmer M, Song WC (2018) Blocking properdin prevents complement-mediated hemolytic uremic syndrome and systemic thrombophilia. J Am Soc Nephrol 29:1928–1937. https://doi.org/10.1681/ASN.2017121244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kimura Y, Zhou L, Miwa T, Song WC (2010) Genetic and therapeutic targeting of properdin in mice prevents complement-mediated tissue injury. J Clin Investig 120:3545–3554. https://doi.org/10.1172/jci41782

    Article  CAS  PubMed  Google Scholar 

  26. Miwa T, Sato S, Gullipalli D, Nangaku M, Song WC (2013) Blocking properdin, the alternative pathway, and anaphylatoxin receptors ameliorates renal ischemia-reperfusion injury in decay-accelerating factor and CD59 double-knockout mice. J Immunol 190:3552–3559. https://doi.org/10.4049/jimmunol.1202275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang Y, Miwa T, Ducka-Kokalari B, Redai IG, Sato S, Gullipalli D, Zangrilli JG, Haczku A, Song WC (2015) Properdin contributes to allergic airway inflammation through local C3a generation. J Immunol 195:1171–1181. https://doi.org/10.4049/jimmunol.1401819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Harpel PC, Cooper NR (1975) Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin. J Clin Investig 55:593–604. https://doi.org/10.1172/JCI107967

    Article  CAS  PubMed  Google Scholar 

  29. Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T (2000) Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 165:2637–2642. https://doi.org/10.4049/jimmunol.165.5.2637

    Article  CAS  PubMed  Google Scholar 

  30. de Agostini A, Lijnen HR, Pixley RA, Colman RW, Schapira M (1984) Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. J Clin Investig 73:1542–1549. https://doi.org/10.1172/JCI111360

    Article  PubMed  Google Scholar 

  31. Nickel KF, Long AT, Fuchs TA, Butler LM, Renne T (2017) Factor XII as a therapeutic target in thromboembolic and inflammatory diseases. Arterioscler Thromb Vasc Biol 37:13–20. https://doi.org/10.1161/ATVBAHA.116.308595

    Article  CAS  PubMed  Google Scholar 

  32. Marais AD (2019) Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease. Pathology 51:165–176. https://doi.org/10.1016/j.pathol.2018.11.002

    Article  CAS  PubMed  Google Scholar 

  33. Boisvert WA, Spangenberg J, Curtiss LK (1995) Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation. J Clin Investig 96:1118–1124. https://doi.org/10.1172/JCI118098

    Article  CAS  PubMed  Google Scholar 

  34. Ginsberg HN, Le NA, Goldberg IJ, Gibson JC, Rubinstein A, Wang-Iverson P, Norum R, Brown WV (1986) Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J Clin Investig 78:1287–1295. https://doi.org/10.1172/JCI112713

    Article  CAS  PubMed  Google Scholar 

  35. Aalto-Setala K, Fisher EA, Chen X, Chajek-Shaul T, Hayek T, Zechner R, Walsh A, Ramakrishnan R, Ginsberg HN, Breslow JL (1992) Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. J Clin Investig 90:1889–1900. https://doi.org/10.1172/JCI116066

    Article  CAS  PubMed  Google Scholar 

  36. Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC (1995) Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 15:963–971. https://doi.org/10.1161/01.atv.15.7.963

    Article  CAS  PubMed  Google Scholar 

  37. Brown RJ, Lagor WR, Sankaranaravanan S, Yasuda T, Quertermous T, Rothblat GH, Rader DJ (2010) Impact of combined deficiency of hepatic lipase and endothelial lipase on the metabolism of both high-density lipoproteins and apolipoprotein B-containing lipoproteins. Circ Res 107:357–364. https://doi.org/10.1161/CIRCRESAHA.110.219188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ooi EM, Watts GF, Chan DC, Chen MM, Nestel PJ, Sviridov D, Barrett PH (2008) Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome. Diabetes Care 31:1656–1661. https://doi.org/10.2337/dc08-0358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mendivil CO, Rimm EB, Furtado J, Chiuve SE, Sacks FM (2011) Low-density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease. Circulation 124:2065–2072. https://doi.org/10.1161/CIRCULATIONAHA.111.056986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, Post W, McLenithan JC, Bielak LF, Peyser PA, Mitchell BD, Miller M, O’Connell JR, Shuldiner AR (2008) A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 322:1702–1705. https://doi.org/10.1126/science.1161524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Crosby J, Peloso GM, Auer PL, Crosslin DR, Stitziel NO, Lange LA, Lu Y, Tang ZZ, Zhang H, Hindy G, Masca N, Stirrups K, Kanoni S, Do R, Jun G, Hu Y, Kang HM, Xue C, Goel A, Farrall M, Duga S, Merlini PA, Asselta R, Girelli D, Olivieri O, Martinelli N, Yin W, Reilly D, Speliotes E, Fox S, Hveem K, Holmen OL, Nikpay M, Farlow DN, Assimes TL, Franceschini N, Robinson J, North KE, Martin LW, DePristo M, Gupta N, Escher SA, Jansson JH, Van Zuydam N, Palmer CN, Wareham N, Koch W, Meitinger T, Peters A, Lieb W, Erbel R, Konig IR, Kruppa J, Degenhardt F, Gottesman O, Bottinger EP, O’Donnell CJ, Psaty BM, Ballantyne CM, Abecasis G, Ordovas JM, Melander O, Watkins H, Orho-Melander M, Ardissino D, Loos RJ, McPherson R, Willer CJ, Erdmann J, Hall AS, Samani NJ, Deloukas P, Schunkert H, Wilson JG, Kooperberg C, Rich SS, Tracy RP, Lin DY, Altshuler D, Gabriel S, Nickerson DA, Jarvik GP, Cupples LA, Reiner AP, Boerwinkle E, Kathiresan S (2014) Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 371:22–31. https://doi.org/10.1056/NEJMoa1307095

    Article  CAS  Google Scholar 

  42. Brouillette CG, Anantharamaiah GM, Engler JA, Borhani DW (2001) Structural models of human apolipoprotein A-I: a critical analysis and review. Biochim Biophys Acta 1531:4–46. https://doi.org/10.1016/s1388-1981(01)00081-6

    Article  CAS  PubMed  Google Scholar 

  43. Duffy D, Rader DJ (2009) Update on strategies to increase HDL quantity and function. Nat Rev Cardiol 6:455–463. https://doi.org/10.1038/nrcardio.2009.94

    Article  PubMed  Google Scholar 

  44. Cho KH, Park SH, Han JM, Kim HC, Choi YK, Choi I (2006) ApoA-I mutants V156K and R173C promote anti-inflammatory function and antioxidant activities. Eur J Clin Investig 36:875–882. https://doi.org/10.1111/j.1365-2362.2006.01737.x

    Article  CAS  Google Scholar 

  45. Cho KH (2011) Enhanced delivery of rapamycin by V156K-apoA-I high-density lipoprotein inhibits cellular proatherogenic effects and senescence and promotes tissue regeneration. J Gerontol A Biol Sci Med Sci 66:1274–1285. https://doi.org/10.1093/gerona/glr169

    Article  CAS  PubMed  Google Scholar 

  46. Ferretti G, Bacchetti T, Bicchiega V, Curatola G (2002) Effect of human Apo AIV against lipid peroxidation of very low density lipoproteins. Chem Phys Lipids 114:45–54. https://doi.org/10.1016/s0009-3084(01)00201-8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

Thanks the Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences for donating B. microti in this experiment.

Funding

This work was supported by the Natural Science Fund for Distinguished Young Scholars of Hebei Normal University (No. L2017J04).

Author information

Author notes

  1. Hui Wang & Jingze Liu

    Present address: Hebei Normal University, 20 nanerhuan east road, Shijiazhuang, Hebei, People’s Republic of China

  2. Xiaoshuang Wang, Shuguang Ren and Xiaohong Yang have contributed equally to this work.

Authors and Affiliations

  1. Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, 050024, Hebei, People’s Republic of China

    Xiaoshuang Wang, Shuguang Ren, Abolfazl Masoudi, Xiaomin Xue, Mengxue Li, Hongxia Li, Xiaojing Zhang, Hui Wang & Jingze Liu

  2. The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, People’s Republic of China

    Shuguang Ren

  3. Department of Pathogenic Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, 050017, Hebei, People’s Republic of China

    Xiaohong Yang

  4. State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, People’s Republic of China

    Xiaohong Yang

Authors
  1. Xiaoshuang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuguang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abolfazl Masoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaomin Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mengxue Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hongxia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaojing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jingze Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HW designed experiments and wrote the initial manuscript. XW, SR, XY, AM, XX performed experiments. ML, HL, XZ prepared figures. JL designed experiments and correction of the manuscript.

Corresponding authors

Correspondence to Hui Wang or Jingze Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Ren, S., Yang, X. et al. Exploration of Serum Marker Proteins in Mice Induced by Babesia microti Infection Using a Quantitative Proteomic Approach. Protein J 40, 119–130 (2021). https://doi.org/10.1007/s10930-020-09952-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10930-020-09952-7

Keywords

Search

Navigation