DOI QR코드

DOI QR Code

The protective effects of BMSA1 and BMSA5-1-1 proteins against Babesia microti infection

  • Yu Chun Cai (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology) ;
  • Chun Li Yang (Department of Clinical Research, the 903rd Hospital of PLA) ;
  • Peng Song (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology) ;
  • Muxin Chen (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology) ;
  • Jia Xu Chen (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology)
  • Received : 2023.07.08
  • Accepted : 2024.01.23
  • Published : 2024.02.29

Abstract

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 ㎍/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0±3.0%, and 48.0±2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

Keywords

Acknowledgement

The Shanghai Natural Science Foundation fund (21ZR1469900), Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (2023-2025) Key Discipline Project (No. GWVI-11.1-12), the National Parasitic Resources Center, and the Ministry of Science and Technology fund (NPRC-2019-194-30) supported this work.

References

  1. Vannier E, Krause PJ. Human babesiosis. N Engl J Med 2012;366(25):2397-2407. https://doi.org/10.1056/NEJMra1202018 
  2. Esernio Jenssen D, Scimeca PG, Benach JL, Tenenbaum MJ. Transplacental/perinatal babesiosis. J Pediatr 1987;110(4):570-572. https://doi.org/10.1016/s0022-3476(87)80552-8 
  3. Fox LM, Wingerter S, Ahmed A, Arnold A, Chou J, et al. Neonatal babesiosis: case report and review of the literature. Pediatr Infect Dis J 2006;25(2):169-173. https://doi.org/10.1097/01.inf.0000195438.09628.b0 
  4. Gubernot DM, Nakhasi HL, Mied PA, Asher DM, Epstein JS, et al. Transfusion-transmitted babesiosis in the United States: summary of a workshop. Transfusion 2009;49(12):2759-2771. https://doi:10.1111/j.1537-2995.2009.02429.x 
  5. Hunfeld KP, Hildebrandt A, Gray JS. Babesiosis: recent insights into an ancient disease. Int J Parasitol 2008;38 (11):1219-1237. https://doi.org/10.1016/j.ijpara.2008.03.001 
  6. Krause PJ, Telford SR 3rd, Ryan R, Hurta AB, Kwasnik I, et al. Geographical and temporal distribution of babesial infection in Connecticut. J Clin Microbiol 1991;29(1):1-4. https://doi.org/10.1128/jcm.29.1.1-4.1991 
  7. Gorenflot A, Moubri K, Precigout E, Carcy B, Schetters TP. Human babesiosis. Ann Trop Med Parasitol 1998;92(4):489-501. https://doi.org/10.1080/00034989859465 
  8. Gelfand JA, Callahan MV. Babesiosis. Curr Clin Top Infect Dis 1998;18:201-216. 
  9. Magnarelli LA, Ijdo JW, Anderson JF, Padula SJ, Flavell RA, et al. Human exposure to a granulocytic Ehrlichia and other tick-borne agents in Connecticut. J Clin Microbiol 1998;36(10):2823- 2827. https://doi.org/10.1128/JCM.36.10.2823-2827.1998 
  10. Jiang JF, Zheng YC, Jiang RR, Li H, Huo QB, et al. Epidemiological, clinical, and laboratory characteristics of 48 cases of "Babesia venatorum" infection in China: a descriptive study. Lancet Infect Dis 2015;15(2):196-203. https://doi.org/10.1016/S1473-3099(14)71046-1 
  11. Carcy B, Precigout E, Schetters T, Gorenflot A. Genetic basis for GPI-anchor merozoite surface antigen polymorphism of Babesia and resulting antigenic diversity. Vet Parasitol 2006;138(1-2):33-49. https://doi.org/10.1016/j.vetpar.2006.01.038 
  12. Nathaly Wieser S, Schnittger L, Florin-Christensen M, Delbecq S, Schetters T. Vaccination against babesiosis using recombinant GPI-anchored proteins. Int J Parasitol 2019,49(2):175-181. https://doi.org/10.1016/j.ijpara.2018.12.002 
  13. Luo Y, Jia H, Terkawi MA, Goo YK, Kawano S, et al. Identification and characterization of a novel secreted antigen 1 of Babesia microti and evaluation of its potential use in enzyme-linked immunosorbent assay and immunochromatographic test. Parasitol Int 2011;60(2):119-125. https://doi.org/10.1016/j.parint.2010.11.001 
  14. Cornillot E, Dassouli A, Pachikara N, Lawres L, Renard I, et al. A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti. Transfusion 2016;56(8):2085-2099. https://doi.org/10.1111/trf.13640 
  15. Thekkiniath J, Mootien S, Lawres L, Perrin BA, Gewirtz M, et al. BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti Infection. J Clin Microbiol 2018;56(10):e00067-18. https://doi.org/10.1128/JCM.00067-18 
  16. Cai YC, Wu F, Hu W, Chen J, Chen SH, et al. Molecular Characteriz red blood cell ation of Babesia microti Seroreactive Antigen 5-1-1 and Development of Rapid Detection Methods for Anti-B. microti Antibodies in Serum. Acta Trop 2018;185:371-379. https://doi.org/10.1016/j.actatropica.2018.03.020 
  17. Zhang Y, Jiang N, Lu H, Hou N, Piao X, et al. Proteomic analysis of Plasmodium falciparum schizonts reveals heparin-binding merozoite proteins. J Proteome Res 2013;12(5):2185-2193. https://doi.org/10.1021/pr400038j 
  18. Cai YC, Yang CL, Hu W, Song P, Xu B, et al. Molecular characterization and immunological evaluation of truncated Babesia microti rhoptry neck protein 2 (BmRON2) as a vaccine candidate. Front Immunol 2021;12:616343. https://doi.org/10.3389/fimmu.2021.616343 
  19. Vogt AM, Pettersson F, Moll K, Jonsson C, Normark J, et al. Release of sequestered malaria parasites upon injection of a glycosaminoglycan. PLoS Pathogens 2006;2(9):e100. https://doi.org/10.1371/journal.ppat.0020100 
  20. Boyle MJ, Richards JS, Gilson PR, Chai W, Beeson JG. Interactions with heparin-like molecules during erythrocyte invasion by P. falciparum merozoites. Blood 2010;115(22):4559-4568. https://doi.org/10.1182/blood-2009-09-243725 
  21. Homer MJ, Aguilar-Delfin I, Telford SR 3rd, Krause PJ, Persing DH. Babesiosis. Clin Microbiol Rev 2000;13(3):451-469. https://doi.org/10.1128/CMR.13.3.451 
  22. Sharma P, Bhargava M, Sukhachev D, Datta S, Wattal C. LH750 hematology analyzers to identify malaria and dengue and distinguish them from other febrile illnesses. Int J Lab Hematol 2014;36(1):45-55. https://doi.org/10.1111/ijlh.12116 
  23. Yu-Chun C, Shao-Hong C, Chun-Li Y, Zhi-Xin Z, Hao L, et al. Dynamic of routine blood test in BALB/c mice with Babesia microti infection. Chin J Schisto Control 2018;30(3):300-306 (in Chinese). https://doi.org/10.16250/j.32.1374.2018119 
  24. Hemmer RM, Ferrick DA, Conrad PA. Up-regulation of tumor necrosis factor-alpha and interferon-gamma expression in the spleen and lungs of mice infected with the human Babesia isolate WA1. Parasitol Res 2000;86(2):121-128. https://doi.org/10.1007/s004360050021 
  25. Goff WL, Johnson WC, Parish SM, Barrington GM, Elsasser TH, et al. IL-4 and IL-10 inhibition of IFN-gamma- and TNFalpha-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites. Vet Immunol Immunopathol 2002;84(3-4):237-251. https://doi.org/10.1016/s0165-2427(01)00413-5 
  26. Stich RW, Shoda LK, Dreewes M, Adler B, Jungi TW, et al. Stimulation of nitric oxide production in macrophages by Babesia bovis. Infect Immun 1998;66(9):4130-4136. https://doi.org/10.1128/IAI.66.9.4130-4136.1998 
  27. Clawson ML, Paciorkowski N, Rajan TV, La Vake C, Pope C, et al. Cellular immunity, but not gamma interferon, is essential for resolution of Babesia microti infection in BALB/c mice. Infect Immun 2002;70(9):5304-5306. https://doi.org/10.1128/IAI.70.9.5304-5306.2002 
  28. Buddle BM, Wedlock DN, Denis M, Skinner MA. Identification of immune response correlates for protection against bovine tuberculosis. Vet Immunol Immunopathol 2005;108(1-2):45-51. https://doi.org/10.1016/j.vetimm.2005.08.002