EVALUATION OF BRAIN MICROGLIA PROLIFERATION AS A RESPONSE TO DBL2β-PFEMP1 RECOMBINANT PROTEIN IMMUNIZATION IN WISTAR RAT
DOI:
https://doi.org/10.21776/ub.mnj.2025.011.01.04Keywords:
brain, DBL2β-PfEMP1, immunization, microglia, Plasmodium falciparumAbstract
Background: In the malaria vaccine study, Duffy binding-like 2β Plasmodium falciparum erythrocyte membrane protein 1 (DBL2β-PfEMP1) could induce the IgG and CD4+production. Antibody to DBL2β-PfEMP1 reduces the risk of developing severe malaria through the blockade of cytoadherence and destruction of rosette formation. During the process of antibody formation after immunization, the released peripheral cytokines have the potential to cause blood-brain barrier disruption resulting in the activation and proliferation of brain microglia as primary innate immune cells leading to neuroinflammation.
Objective: This study aims to evaluate brain microglia proliferation as a response to recombinant protein DBL2β-PfEMP1 immunization in Wistar rats.
Methods: Wistar rats were injected subcutaneously with recombinant protein DBL2β-PfEMP1 at doses of 100, 150, and 200 µg/kgBW on days 0, 21, and 42. Rats were euthanized on day 56. Brain histopathological slides were prepared and stained using hematoxylin-eosin. Histological examination was performed using a microscope at 400X magnification and documented using an AmScope microscope digital camera. Brain microglia were calculated using Fiji Image-J. The data were statistically analyzed using the Kruskal-Wallis test.
Results: The average number of brain microglia in both the control and treatment groups was 82–88. There was no significant difference in brain microglia number between the control and treatment groups (p>0.05) after recombinant protein DBL2β-PfEMP1 immunization.
Conclusion: Recombinant protein DBL2β-PfEMP1 immunization does not provoke the proliferation of brain microglia in Wistar rats. This suggests that the protein does not have the potential to cause neuroinflammation.
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References
Smith JD, Rowe JA, Higgins MK, Lavstsen T. Malaria’s deadly grip: Cytoadhesion of Plasmodium falciparum-infected erythrocytes. Cell Microbiol; 2013. 15(12):1976–83. DOI: 10.1111/cmi.12183.
Zekar L, St. Pierre L. Plasmodium falciparum Malaria. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555962/
Adukpo S, Kusi KA, Ofori MF, Tetteh JKA, Amoako-Sakyi D, Goka BQ, et al. High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria. PLoS One; 2013. 8(12):e84181.
DOI: 10.1371/journal.pone.0084181.
Gullingsrud J, Saveria T, Amos E, Duffy PE, Oleinikov AV. Structure-Function-Immunogenicity Studies of PfEMP1 Domain DBL2βPF11_0521, a Malaria Parasite Ligand for ICAM-1. PLoS One; 2013. 8(4):e61323. DOI: 10.1371/journal.pone.0061323.
Jensen AR, Adams Y, Hviid L. Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. Immunol Rev; 2020. 293(1):230–52. DOI: 10.1111/imr.12805.
Barros Pinto MP, Marques G. Severe malaria. Infection; 2020. 48(1):143–6. DOI: 10.1007/s15010-019-01350-1.
Lenz KM, Nelson LH. Microglia and beyond: Innate immune cells as regulators of brain development and behavioral function. Front Immunol; 2018. 9:698.
DOI: 10.3389/fimmu.2018.00698.
Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol; 2018. 18(4):225–42. DOI: 10.1038/nri.2017.125.
Capuccini B, Lin J, Talavera-López C, Khan SM, Sodenkamp J, Spaccapelo R, et al. Transcriptomic profiling of microglia reveals signatures of cell activation and immune response during experimental cerebral malaria. Sci Rep; 2016. 6:39258.
DOI: 10.1038/srep39258.
Xu L, He D, Bai Y. Microglia-Mediated inflammation and neurodegenerative disease. Mol Neurobiol; 2016. 53(10):6709–15. DOI: 10.1007/s12035-015-9696-5.
Mbagwu SI, Lannes N, Walch M, Filgueira L, Mantel PY. Human microglia respond to malaria-induced extracellular vesicles. Pathogens; 2020. 9(1):21.
DOI: 10.3390/pathogens9010021.
Andoh NE, Gyan BA. The potential roles of glial cells in the neuropathogenesis of cerebral malaria. Front Cell Infect Microbiol; 2021. 11:741370.
DOI: 10.3389/fcimb.2021.741370.
World Health Organization. World Malaria Report 2021. Geneva: World Health Organization; 2021. Available from:
https://www.who.int/publications/i/item/9789240040496.
European Medicines Agency. Mosquirix: EPAR - Product Information; 2015. Available from: https://www.ema.europa.eu/en/documents/product-information/mosquirix-epar-product-information_en.pdf.
Sulistyaningsih E. Vaksin Malaria: Perkembangan Generasi Vaksin, Kandidat Protein Untuk Vaksin, dan Tantangannya. Indonesia: UPT Penerbitan Universitas Jember; 2020.
Laurens MB. RTS,S/AS01 vaccine (Mosquirix™): An overview. Hum Vaccin Immunother; 2020. 16(3):480–9. DOI: 10.1080/21645515.2019.1669415.
Rachmania S, Sulistyaningsih E, Ratna Dewi AAI. Recombinant DBL2β-PfEMP1 of the Indonesian Plasmodium falciparum induces immune responses in Wistar rats. J Taibah Univ Med Sci; 2021. 16(3):422–30. DOI: 10.1016/j.jtumed.2020.12.007.
Tessema SK, Utama D, Chesnokov O, Hodder AN, Lin CS, Harrison GLA, et al. Antibodies to intercellular adhesion molecule 1-binding Plasmodium falciparum erythrocyte membrane protein 1-DBLβ are biomarkers of protective immunity to malaria in a cohort of young children from Papua New Guinea. Infect Immun; 2018. 86(8):e00217-18. DOI: 10.1128/IAI.00217-18.
Chan JA, Fowkes FJI, Beeson JG. Surface antigens of Plasmodium falciparum-infected erythrocytes: Cell Mol Life Sci; 2014. 71(19):3633–57. DOI: 10.1007/s00018-014-1612-7.
Hoogland ICM, Houbolt C, van Westerloo DJ, van Gool WA, van de Beek D. Systemic inflammation and microglial activation: Systematic review of animal experiments. J Neuroinflammation [Internet]; 2015. 12(1):1–13. DOI: 10.1186/s12974-015-0332-6
Putri Dwi Ari Santi, Sulistyaningsih Erma, Kusuma Irawan Fajar, Dewi R. Total leukocyte count in Rattus norvegicus after Duffy binding-like 2β-Plasmodium falciparum erythrocyte membrane protein 1 recombinant protein injection: The way to a peptide-based malaria vaccine development. Biomol Health Sci J; 2022. 5(2):71–6.
DOI: 10.4103/bhsj.bhsj_22_22.
Garman RH. Histology of the Central Nervous System. Toxicol Pathol; 2011. 39(1):22–35.
DOI: 10.1177/0192623310389621.
Mescher AL. Junqueira’s Basic Histology Text & Atlas. 13th ed. New York: McGraw-Hill Education; 2013. p. 160–74. DOI: 10.1036/9780071802788.
Taber KS. The use of Cronbach’s alpha when developing and reporting research instruments in science education. Res Sci Educ; 2018. 48(6):1273–96. DOI: 10.1007/s11165-016-9602-2.
Nicholson LB. The immune system. Essays Biochem; 2016. 60(3):275–301. DOI: 10.1042/EBC20160003.
Daneman R, Prat A. The blood–brain barrier. Cold Spring Harb Perspect Biol; 2015. 7(1):a020412.
DOI: 10.1101/cshperspect.a020412.
Bellettato CM, Scarpa M. Possible strategies to cross the blood–brain barrier. Ital J Pediatr.; 2018. 44(S2):S6. DOI: 10.1186/s13052-018-0462-0.
Galea I. The blood–brain barrier in systemic infection and inflammation. Cell Mol Immunol.; 2021. 18(11):2489–501. DOI: 10.1038/s41423-021-00688-0.
Crews FT, Vetreno RP. Mechanisms of neuroimmune gene induction in alcoholism. Psychopharmacology (Berl); 2016. 233(9):1543–57. DOI: 10.1007/s00213-016-4299-0
Kierdorf K, Prinz M. Factors regulating microglia activation. Front Cell Neurosci.; 2013. 7:44.
DOI: 10.3389/fncel.2013.00044.
Giannotta G, Giannotta N. Vaccines and neuroinflammation. Int J Public Health Safety; 2018. 3(3):1–4. DOI: 10.23937/ijphs-3-1130210.
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