Toll-Like Receptor Activation and B Cell Maturation Via MyD88-Dependent Pathway Under Hyperglycemia Condition

Riandini Aisyah(1*), Safari Wahyu Jatmiko(2)

(1) Department of Biomedical Sciences, Faculty of Medicine, Universitas Muhammadiyah Surakarta, Campus IV UMS Gonilan Kartasura, Gonilan, Sukoharjo, Kabupaten Sukoharjo, Jawa Tengah 57169
(2) Clinical Pathology Laboratory, Faculty of Medicine, Universitas Muhammadiyah Surakarta
(*) Corresponding Author

Abstract

hyperglycemia causes a degenerative syndrome that involves an inflammatory process with an increase in certain proinflammatory cytokines and chemokines which in the process will activate B cells to produce immunoglobulins through several mechanisms. One of the interesting mechanisms is the mechanism via the MyD88 pathway. Objectives: to explore the role of MyD88 adapter protein in Toll-like receptor activation and B cell maturation under hyperglycemia conditions. Methods: a literature review was done to answer the study objectives. Results: Class switching process under hyperglycemia conditions involves activation of NFkB through the inflammatory MyD88-dependent pathway to trigger the expression of TLR and B cell maturation and proliferation as well as antibody production. The MyD88 adapter protein is a protein formed by stimulation of pro-inflammatory cytokines IL-6 and plays a role in the continuation of signals from the TLR and IL-1 pathways. Mature B cell stimulation induces 2 genetic changes in the Ig gene locus, called somatic hypermutation (SHM) and class switch recombination (CSR) to produce antibodies. Changes in immunoglobulin genes occur related to changes in certain DNA segments at the locus of genes where CSR occurs, this gene change requires the role of AID (activated-induced cytidine deaminase) in DNA cleavage. AID in mature B cells is activated by proinflammatory cytokines via induction of NfKB activation via the inflammatory MyD88-dependent pathway. Conclusion: Toll-like receptor activation plays a crucial role in B cell maturation activated by pro-inflammatory cytokine via MyD88 dependent-NFkB activation.

 

Keywords

proinflammatory cytokines; TLR; B cell maturation; MyD88; hyperglicemia

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References

Althwaiqeb, S. A., & Bordoni, B. (2023a). Histology, B Cell Lymphocyte. In NCBI Bookshelf. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK560905/.

Angeli, F., Reboldi, G., Poltronieri, C., Lazzari, L., Sordi, M., Garofoli, M., Bartolini, C., & Verdecchia, P. (2015). Hyperglycemia in acute coronary syndromes: From mechanisms to prognostic implications. Therapeutic Advances in Cardiovascular Disease, 9(6), 412–424. https://doi.org/10.1177/1753944715594528.

Argyropoulos, T., Korakas, E., Gikas, A., Kountouri, A., Kostaridou-Nikolopoulou, S., Raptis, A., & Lambadiari, V. (2021). Stress Hyperglycemia in Children and Adolescents as a Prognostic Indicator for the Development of Type 1 Diabetes Mellitus. Frontiers in Pediatrics, 9, 670976. https://doi.org/10.3389/fped.2021.670976.

Barcelo, A., Gregg, E. W., Gerzoff, R. B., Wong, R., Perez Flores, E., Ramirez-Zea, M., Cafiero, E., Altamirano, L., Ascencio Rivera, M., De Cosio, G., De Maza, M. D., Del Aguila, R., Emanuel, E., Gil, E., Gough, E., Jenkins, V., Orellana, P., Palma, R., Palomo, R., … for the CAMDI Collaborative Study Group. (2012). Prevalence of Diabetes and Intermediate Hyperglycemia Among Adults From the First Multinational Study of Noncommunicable Diseases in Six Central American Countries. Diabetes Care, 35(4), 738–740. https://doi.org/10.2337/dc11-1614.

Berger, E. A., Carion, T. W., Jiang, Y., Liu, L., Chahine, A., Walker, R. J., & Steinle, J. J. (2016). β‐Adrenergic receptor agonist, compound 49b, inhibits TLR4 signaling pathway in diabetic retina. Immunology & Cell Biology, 94(7), 656–661. https://doi.org/10.1038/icb.2016.21.

Chi, X., Li, Y., & Qiu, X. (2020). V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: Mechanism and regulation. Immunology, 160(3), 233–247. https://doi.org/10.1111/imm.13176.

Chia, C. W., Egan, J. M., & Ferrucci, L. (2018). Age-Related Changes in Glucose Metabolism, Hyperglycemia, and Cardiovascular Risk. Circulation Research, 123(7), 886–904. https://doi.org/10.1161/CIRCRESAHA.118.312806.

Corsiero, E., Nerviani, A., Bombardieri, M., & Pitzalis, C. (2016). Ectopic Lymphoid Structures: Powerhouse of Autoimmunity. Frontiers in Immunology, 7. https://doi.org/10.3389/fimmu.2016.00430.

Dasu, M. R., & Martin, S. J. (2014). Toll-like receptor expression and signaling in human diabetic wounds. World Journal of Diabetes, 5(2), 219. https://doi.org/10.4239/wjd.v5.i2.219.

Dendup, T., Feng, X., Clingan, S., & Astell-Burt, T. (2018). Environmental Risk Factors for Developing Type 2 Diabetes Mellitus: A Systematic Review. International Journal of Environmental Research and Public Health, 15(1), 78. https://doi.org/10.3390/ijerph15010078.

Duan, W., Shen, X., Lei, J., Xu, Q., Yu, Y., Li, R., Wu, E., & Ma, Q. (2014). Hyperglycemia, a Neglected Factor during Cancer Progression. BioMed Research International, 2014, 1–10. https://doi.org/10.1155/2014/461917

Friedrich, C., Mamareli, P., Thiemann, S., Kruse, F., Wang, Z., Holzmann, B., Strowig, T., Sparwasser, T., & Lochner, M. (2017). MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium. PLOS Pathogens, 13(5), e1006357. https://doi.org/10.1371/journal.ppat.1006357.

Fuentes-Antrás, J., Ioan, A. M., Tuñón, J., Egido, J., & Lorenzo, Ó. (2014). Activation of Toll-Like Receptors and Inflammasome Complexes in the Diabetic Cardiomyopathy-Associated Inflammation. International Journal of Endocrinology, 2014, 1–10. https://doi.org/10.1155/2014/847827.

Garg, R., Akhade, A. S., Yadav, J., & Qadri, A. (2015). MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG. Innate Immunity, 21(7), 778–783. https://doi.org/10.1177/1753425915599242.

Gebreyes, Y. F., Goshu, D. Y., Geletew, T. K., Argefa, T. G., Zemedu, T. G., Lemu, K. A., Waka, F. C., Mengesha, A. B., Degefu, F. S., Deghebo, A. D., Wubie, H. T., Negeri, M. G., Tesema, T. T., Tessema, Y. G., Regassa, M. G., Eba, G. G., Beyene, M. G., Yesu, K. M., Zeleke, G. T., … Belayneh, A. B. (2018). Prevalence of high bloodpressure, hyperglycemia, dyslipidemia, metabolic syndrome and their determinants in Ethiopia: Evidences from the National NCDs STEPS Survey, 2015. PLOS ONE, 13(5), e0194819. https://doi.org/10.1371/journal.pone.0194819.

Gojda, J., Koudelková, K., Ouřadová, A., Lang, A., Krbcová, M., Gvozdeva, A., Šebo, V., Slagmolen, L., Potočková, J., Tůma, P., Rossmeislová, L., Anděl, M., Karpe, F., & Schlesinger, S. (2023). Severe COVID-19 associated hyperglycemia is caused by beta cell dysfunction: A prospective cohort study. Nutrition & Diabetes, 13(1), 11. https://doi.org/10.1038/s41387-023-00241-7

Gojda, J., Lang, A., Gvozdeva, A., Slagmolen, L., Karpe, F., & Schlesinger, S. (2023). Severe COVID-19 associated hyperglycemia is caused by beta cell dysfunction: A prospective cohort study. October 2022, 1–11. https://doi.org/10.1038/s41387-023-00241-7.

Ham, S. Y., Nam, S. B., Kwak, Y.-L., Kim, T. L., Park, J.-K., & Shim, Y. H. (2019). Age-Related Difference in the Effect of Acute Hyperglycemia on Myocardial Ischemia-Reperfusion Injury. The Journals of Gerontology: Series A. https://doi.org/10.1093/gerona/gly292.

Jatmiko, S. W. (2018). Imunologi Dasar. Surakarta: MUP.

Jatmiko, S. W., & Aisyah, R. (2015). Imunitas Alamiah. Surakarta: UNS Press.

Kiripolsky, J., Romano, R.-A., Kasperek, E. M., Yu, G., & Kramer, J. M. (2020). Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren’s Syndrome. Frontiers in Immunology, 10, 2963. https://doi.org/10.3389/fimmu.2019.02963.

Kolb, H., & Martin, S. (2017). Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes. BMC Medicine, 15(1), 131. https://doi.org/10.1186/s12916-017-0901-x.

Korytkowski, M., McDonnell, M. E., Umpierrez, G. E., & Zonszein, J. (Eds.). (2012). Patient Guide to Managing Hyperglycemia (High Blood Sugar) in the Hospital. The Journal of Clinical Endocrinology & Metabolism, 97(1), 27A-28A. https://doi.org/10.1210/jcem.97.1.zeg27a.

Lai, S.-W., Tan, C.-K., & Ng, K.-C. (2000). Epidemiology of Hyperglycemia in Elderly Persons. Journal of Gerontology: MEDICAL SCIENCE, 55A(5), M257–M259.

Lannoy, V., Côté-Biron, A., Asselin, C., & Rivard, N. (2023). TIRAP, TRAM, and Toll-Like Receptors: The Untold Story. Mediators of Inflammation, 2023, 1–13. https://doi.org/10.1155/2023/2899271.

Lee, P. G., & Halter, J. B. (2017). The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations. Diabetes Care, 40(4), 444–452. https://doi.org/10.2337/dc16-1732.

Li, Y., Liu, Y., Liu, S., Gao, M., Wang, W., Chen, K., Huang, L., & Liu, Y. (2023). Diabetic vascular diseases: Molecular mechanisms and therapeutic strategies. Signal Transduction and Targeted Therapy, 8(1), 152. https://doi.org/10.1038/s41392-023-01400-z.

Meza, C. A., La Favor, J. D., Kim, D.-H., & Hickner, R. C. (2019). Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS? International Journal of Molecular Sciences, 20(15), 3775. https://doi.org/10.3390/ijms20153775.

Mouri, M., & Badireddy, M. (2023). Hyperglycemia. In NCBI Bookshelf (PMID: 28613650). StatPearls Publishing LLC. https://www.ncbi.nlm.nih.gov/books/NBK430900/.

Nedosugova, L. V., Markina, Y. V., Bochkareva, L. A., Kuzina, I. A., Petunina, N. A., Yudina, I. Y., & Kirichenko, T. V. (2022). Inflammatory Mechanisms of Diabetes and Its Vascular Complications. Biomedicines, 10(5), 1168. https://doi.org/10.3390/biomedicines10051168.

Nogueira-Machado, J. A. (2011). HMGB1, TLR and RAGE: a functional tripod that leads to diabetic inflammation. Expert Opin. Ther. Targets, 15(8):1023-1035.

Nouhjah, S., Shahbazian, H., Shahbazian, N., Jahanshahi, A., Jahanfar, S., & Cheraghian, B. (2017). Incidence and Contributing Factors of Persistent Hyperglycemia at 6–12 Weeks Postpartum in Iranian Women with Gestational Diabetes: Results from LAGA Cohort Study. Journal of Diabetes Research, 2017, 1–9. https://doi.org/10.1155/2017/9786436.

Pasquel, F. J., Lansang, M. C., Dhatariya, K., & Umpierrez, G. E. (2021). Management of diabetes and hyperglycaemia in the hospital. The Lancet Diabetes & Endocrinology, 9(3), 174–188. https://doi.org/10.1016/S2213-8587(20)30381-8.

Peng, J., Zheng, H., Wang, X., & Cheng, Z. (2017). Upregulation of TLR4 via PKC activation contributes to impaired wound healing in high-glucose-treated kidney proximal tubular cells. PLOS ONE, 12(5), e0178147. https://doi.org/10.1371/journal.pone.0178147.

Quang Binh, T., Tran Phuong, P., Thi Nhung, B., Dinh Thoang, D., Van Thang, P., Khanh Long, T., & Van Thanh, D. (2012). Prevalence and correlates of hyperglycemia in a rural population, Vietnam: Implications from a cross–sectional study. BMC Public Health, 12(1), 939. https://doi.org/10.1186/1471-2458-12-939.

Rastogi, R., Geng, X., Li, F., & Ding, Y. (2017). NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease. Frontiers in Cellular Neuroscience, 10. https://doi.org/10.3389/fncel.2016.00301.

Suryavanshi, S. V., & Kulkarni, Y. A. (2017). NF-κβ: A Potential Target in the Management of Vascular Complications of Diabetes. Frontiers in Pharmacology, 8, 798. https://doi.org/10.3389/fphar.2017.00798.

Uchiyama, R., Chassaing, B., Zhang, B., & Gewirtz, A. T. (2015). MyD88-mediated TLR signaling protects against acute rotavirus infection while inflammasome cytokines direct Ab response. Innate Immunity, 21(4), 416–428. https://doi.org/10.1177/1753425914547435.

Vazquez, M. I., Catalan-Dibene, J., & Zlotnik, A. (2015). B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine, 74(2), 318–326. https://doi.org/10.1016/j.cyto.2015.02.007.

Wang, L., Wang, J., Fang, J., Zhou, H., Liu, X., & Su, S. B. (2015a). High glucose induces and activates Toll ‑ like receptor 4 in endothelial cells of diabetic retinopathy. Diabetology & Metabolic Syndrome, 1–10. https://doi.org/10.1186/s13098-015-0086-4.

Wang, L., Wang, J., Fang, J., Zhou, H., Liu, X., & Su, S. B. (2015b). High glucose induces and activates Toll-like receptor 4 in endothelial cells of diabetic retinopathy. Diabetology & Metabolic Syndrome, 7(1), 89. https://doi.org/10.1186/s13098-015-0086-4.

Warner, N., & Núñez, G. (2013a). MyD88: A Critical Adaptor Protein in Innate Immunity Signal Transduction. The Journal of Immunology, 190(1), 3–4. https://doi.org/10.4049/jimmunol.1203103.

Warner, N., & Núñez, G. (2013b). MyD88: A Critical Adaptor Protein in Innate Immunity Signal Transduction. The Journal of Immunology, 190(1), 3–4. https://doi.org/10.4049/jimmunol.1203103.

Wu, H., Chen, Z., Xie, J., Kang, L.-N., Wang, L., & Xu, B. (2016). High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications. Mediators of Inflammation, 2016, 1–11. https://doi.org/10.1155/2016/3896147.

Ye, E.-A., & Steinle, J. J. (2016). miR-146a Attenuates Inflammatory Pathways Mediated by TLR4/NF- κ B and TNF α to Protect Primary Human Retinal Microvascular Endothelial Cells Grown in High Glucose. Mediators of Inflammation, 2016, 1–9. https://doi.org/10.1155/2016/3958453.

Zhai, X., Qian, G., Wang, Y., Chen, X., Lu, J., Zhang, Y., Huang, Q., & Wang, Q. (2016). Elevated B Cell Activation is Associated with Type 2 Diabetes Development in Obese Subjects. Cellular Physiology and Biochemistry, 38(3), 1257–1266. https://doi.org/10.1159/000443073.

DOI: 10.23917/bioeksperimen.v10i1.23328

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