Peran Lactosylceramide sebagai Immunomodulator dan Neuroprotectant Terhadap Mycobacterium leprae, Sebuah Inovasi Terapi Adjuvant Lepra Masa Depan
Abstract
Abstrak
Pendahuluan: Lepra masih menjadi masalah kesehatan serius di berbagai negara tropis dengan angka kejadian cukup tinggi. Penyakit akibat infeksi Mycobacterium lepare (M. leprae) tersebut dapat menurunkan kualitas hidup penderitanya karena gangguan penampilan akibat lesi kulit, gangguan aktivitas akibat gangguan neurologis, serta sulitnya pengobatan akibat resistensinya terhadap imunitas tubuh. Oleh karena itu, dibutuhkan suatu inovasi yang dapat membantu penanganan permasalahan neurologis dan resistensi M. leprae terhadap imunitas untuk mempercepat penyembuhan, menangani masalah neurologis akibat leprae, dan meningkatkan kualitas hidup pasien leprae. Pembahasan: Dalam berbagai penelitian, telah dibuktikan bahwa Lipoarabinomannan (LAM) merupakan salah satu komponen lipid dinding sel M. leprae yang juga berperan dalam kerusakan saraf dan resistensi M. leprae terhadap imunitas, sehingga inhibisi terhadap LAM M. leprae dapat menjadi salah satu target terapi tambahan untuk mengurangi kerusakan neuron dan resistensi M. leprae terhadap imunitas tubuh. Sementara itu, berbagai penelitian laiinya juga telah membuktikan bahwa Lactosylceramide (LacCer) mampu mengikat LAM pada berbagai spesies Mycobacterium, termasuk M. leprae sehingga penggunaan LacCer dapat menjadi terapi adjuvant yang sangat potensial dalam menangani kerusakan neuron dan masalah resistensi M. leprae terhadap imunitas sehingga dapat menangani masalah sistem saraf dan mempercepat kesembuhan serta meningkatkan kualitas hidup pasien-pasien lepra. Kesimpulan: LacCer terbukti mampu menjadi terapi adjuvant potensial untuk leprae akibat kemampuannya sebagai neuroprotectant dan immunomodulator dengan mekanismenya dalam mengikat LAM pada dinding sel M. leprae.
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References
2. Das M, Diana D, Wedderburn A, Rajan L, Rao S, Horo I, et al. Molecular epidemiology and transmission dynamics of leprosy among multicase families and case-contact pairs. Int J Infect Dis [Internet]. 2020;96:172–9. Available from: https://doi.org/10.1016/j.ijid.2020.04.064
3. Maymone MBC, Laughter M, Venkatesh S, Dacso MM, Rao PN, Stryjewska BM, et al. Leprosy: Clinical aspects and diagnostic techniques. J Am Acad Dermatol [Internet]. 2020;83(1):1–14. Available from: https://doi.org/10.1016/j.jaad.2019.12.080
4. Kundakci N, Erdem C. Leprosy: A great imitator. Clin Dermatol [Internet]. 2019;37(3):200–12. Available from: https://doi.org/10.1016/j.clindermatol.2019.01.002
5. Da Silva Junior GB, De Francesco Daher E, Da Justa Pires Neto R, Pereira EDB, Meneses GC, AraÚJo SMHA, et al. Leprosy nephropathy: A review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2015;57(1):15–20.
6. Sumangala S, Nikfekr E, George J, Holmes CW. Leprosy neuropathy masquerading as cellulitis. Postgrad Med J. 2019;95(1122):225–6.
7. Balestrino A, Fiaschi P, Riccardi N, Camera M, Anania P, Martinoli C, et al. Neurosurgical treatment of leprosy neuropathy in a low-incidence, European country. Neurol Sci. 2019;5–9.
8. Jenish Bhandari, Mashal Awais BARVG. Leprosy. StatPearls. 2021.
9. Oo YM, Paez A, Brown R. Leprosy: A rare case of infectious peripheral neuropathy in the United States. IDCases [Internet]. 2020;20:e00765. Available from: https://doi.org/10.1016/j.idcr.2020.e00765
10. Angst DBM, Pinheiro RO, Vieira JS da S, Cobas RA, Hacker M de AVB, Pitta IJR, et al. Cytokine Levels in Neural Pain in Leprosy. Front Immunol. 2020;11(January):1–9.
11. Madigan CA, Cambier CJ, Kelly-Scumpia KM, Scumpia PO, Cheng TY, Zailaa J, et al. A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy. Cell. 2017;170(5):973-985.e10.
12. Prakoeswa CRS, Wahyuni R, Iswahyudi, Adriaty D, Yusuf I, Sutjipto, et al. Expression profile of Rab5, Rab7, tryptophan aspartate-containing coat protein, leprae lipoarabinomannan, and phenolic glycolipid-1 on the failure of the phagolysosome process in macrophages of leprosy patients as a viability marker of Mycobacterium lepra. Int J Mycobacteriology [Internet]. 2016;5(2):155–63. Available from: http://dx.doi.org/10.1016/j.ijmyco.2016.02.001
13. Kaur G, Kaur J. Multifaceted role of lipids in Mycobacterium leprae. Future Microbiol. 2017;12(4):315–35.
14. Ma Y, Pei Q, Zhang L, Lu J, Shui T, Chen J, et al. Live mycobacterium leprae inhibits autophagy and apoptosis of infected macrophages and prevents engulfment of host cell by phagocytes. Am J Transl Res. 2018;10(9):2929–39.
15. Thiago Gomes Toledo Pinto, Leonardo Ribeiro Batista-Silva, Rychelle Clayde Affonso Medeiros FAL and MOM. Type I interferons, autophagy and host metabolism in leprosy. Front Immunol. 2018;9(APR):1–11.
16. Barbosa MG de M, Silva BJ de A, Assis TQ, Prata RB da S, Ferreira H, Andrade PR, et al. Autophagy impairment is associated with increased inflammasome activation and reversal reaction development in multibacillary leprosy. Front Immunol. 2018;9(JUN).
17. Bahia El Idrissi N, Das PK, Fluiter K, Rosa PS, Vreijling J, Troost D, et al. M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator. Acta Neuropathol. 2015;129(5):653–67.
18. Nahas AA, Lima MI de S, Goulart IMB, Goulart LR. Anti-lipoarabinomannan-specific salivary IgA as prognostic marker for leprosy reactions in patients and cellular immunity in contacts. Front Immunol. 2018;9(MAY):1–7.
19. El Idrissi NB, Iyer AM, Ramaglia V, Rosa PS, Soares CT, Baas F, et al. In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy lesional skin. PLoS One. 2017;12(5):1–19.
20. Hitoshi Nakayama MN, Suzuki A, Iwabuchi K, Inokuchi J-I. The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems.pdf. FEBS Lett. 2018;592(23):3921–42.
21. Nakayama H, Kurihara H, Morita YS, Kinoshita T, Mauri L, Prinetti A, et al. Lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils. Sci Signal. 2016;9(449).
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