Perfil de citocinas na patogênese da infecção do vírus Linfotrópico de células T humanas HTLV-1 / Cytokine profile in the pathogenesis of HTLV-1 human T- Cell Lymphotropic virus infection

Authors

  • Marcos Daniel Mendes Padilha
  • Vitória Beatriz de Jesus Viana
  • Oscar David Albito Balcazar
  • Adriana Fernanda Albito Balcázar
  • Gabriela Anabel Aguilar Albito
  • Andreza Juliana Moreira da Costa
  • Maritza del Cisne Albito Balcazar
  • Rosimar Neris Martins Feitosa

DOI:

https://doi.org/10.34119/bjhrv5n4-029

Keywords:

infecção pelo vírus Linfotrópico T Humano 1, Leucemia-Linfoma de Células T do Adulto, anticorpos antivírus I da Leucemia de Células T do adulto, antígenos de deltaretrovírus.

Abstract

Introdução: Identificado em 1980 o HTLV-1 foi o primeiro retrovírus relacionado a neoplasias hematológicas em seres humanos, contribuindo para quadros severos de LTA, LLTA e PETMAH. As oncoproteínas do vírus HBZ e TAX levam a imunodesregulação e oncogênese de pacientes comprometidos. Objetivos: Elucidar o perfil de citocinas na patogênese do HTLV-1 e possíveis mecanismos para modelos imunoterapêuticos. Métodos: Se trata de uma revisão descritiva com análise sistemática, 102 artigos foram selecionados e apenas 54 incluídos, as palavras-chave foram padronizadas de acordo com o DeCS e os artigos categorizados para leitura na íntegra, utilizamos o fluxograma prisma para triagem e seleção dos artigos. Resultados e Discussão: Os altos níveis de IL-10 em pacientes LTA tem sido implicados na imunossupressão grave, CXCL9 e CXCL10 estão associadas ao aumento de células CD8⁺ e inflamação na medula espinhal, CCL3 afeta a inflamação do SNC através de macrófagos e astrócitos, a secreção de IFNγ contribui diretamente para o perfil de citocinas plasmáticas em PETMAH, a IL-6 induz a produção excessiva de VEGF, levando a angiogênese aumentada em tecidos sinoviais de artrite reumatóide relacionada ao HTLV-1. O TNFβ demonstrou promover a tumorigênese induzindo NF-kβ e IL-1β tem sido relacionada a inflamação crônica no SNC na PETMAH. Conclusão: O perfil imunopatológico imposto pelo HTLV-1 contribui para superexpressão de citocinas levando aos quadros de PETMAH e LTA. Citocinas IL-10, CXCL-9, CXCL-10, IFNs, IL-6 em combinação com adjuvantes podem estabelecer modelos eficazes para estudos em fase teste e contribuir com tratamentos terapêuticos futuros.

References

AARREBERG, L. D.; WILKINS, C.; RAMOS, H. J. et al. Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses. mBIO. 2018; 9(2):1-14. doi: 10.1128/mBio.00342-18.

AGHAJANIAN, S.; TEYMOORI-TAD, M.; MOLAVERDI, G. et al. Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis. Frontiers in Microbiology. 2020; 11(614940):1-23. doi: 10.3389/fmicb.2020.614940.

ANDO, H.; SATO, T.; TOMARU, U. et al. Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy. Brain. 2013; 136(9):1-12. doi: 10.1093/brain/awt183.

BANISOR, I.; LEIST, T. P.; KALMAN, B. Involvement of beta-chemokines in the development of inflammatory demyelination. Journal of Neuroinflammation. 2005; 2(7):1-14. doi: 10.1186/1742-2094-2-7.

BELLVER-LANDETE, V.; BRETHEAU, F.; MAILHOT, B. et al. Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury. Nature Communications. 2019; 10(518):1-18. doi: 10.1038/s41467-019-08446-0.

BUHRMANN, C.; YAZDI, M.; POPPER, B. et al. Induction of the Epithelial-to-Mesenchymal Transition of Human of Human Colorectal Cancer by Human TNF-β (Lymphotoxin) and its Reversal by Resveratol. Nutrients. 2019; 11(3):1-19. doi: 10.3390/nu11030704.

CHEN, S.; ISHII, N.; INE, S. et al. Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells. International Immunology. 2006; 18(2):269-277. doi: 10.1093/intimm/dxh366.

DINARELLO, C. A. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunological Reviews. 2018; 281(1):8-27. doi: 10.1111/imr.12621.

DONADO, C. A.; CAO, A. B.; SIMMONS, D. P. et al. A Two-Cell Model For IL-1β Release Mediated by Death-Receptor Signaling. Cell. 2020; 31(1):1-42. doi: 10.1016/j.celrep.2020.03.030.

DUNST, J.; KAMENA, F.; MATUSCHEWSKI, K. Cytokines and Chemokines in Cerebral Malaria Pathogenesis. Frontiers in Cellular and Infection Microbiology. 2017; 7(324):1-16. doi: 10.3389/fcimb.2017.00324.

EDWARDS, D.; FENIZIA, C.; GOLD, H. et al. Orf-I and Orf-II-encoded proteins in HTLV-1 infection and persistence. Viruses. 2011; 861-885. doi: 10.3390/v3060861.

EECKHOUT, B. V. D.; TAVERNIER, J.; GERLO, S. Interleukin-1 as Innate Mediator of T Cell Immunity. Frontiers Immunity. 2021; 11(621931):1-26. doi: 10.3389/fimmu.2020.621931.

EINSIEDEL, L.; CHIONG, F.; JERSMANN, H. et al. Human T-cell leukaemia virus type 1 associated pulmonary disease: clinical and pathological features of an under-recognised complication of HTLV-1 infction. Retrovirology. 2021; 18(1):1-13. doi: https://doi.org/10.1186/s12977-020-00543-z.

FUKUI, S.; NAKAMURA, H.; TAKAHASHI, Y. et al. Tumor necrosis factor alpha inhibitors have no effect on a human T-lymphotropic virus type-I (HTLV-1)-infected cell line from patients with HTLV-1-associated myelopathy. BMC Immunology. 2017; 18(7):1-11. doi: 10.1186/s12865-017-0191-2.

FUTSCH, N.; PRATES, G.; MAHIEUX, R. et al. Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases. Viruses. 2018; 10(12):1-17. doi: 10.3390/v10120691.

GARCÍA-HUIDOBRO, I.; CÁRDENAS, C.; MOLGÓ, M. et al. Manifestaciones cutáneas en donantes de sangre portadores de HTLV-1 en comparación con donantes de sangre no portadores de HTLV-1. Rev. Med. Chile. 2014; 142: 859:866. doi: http://dx.doi.org/10.4067/S0034-98872014000700006.

GUBERNATOVARA, E. O.; POLINOVA, A. I.; PETROPAVLOVSKIY, M. M. et al. Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice. Cancers. 2021; 13(8):1-25. doi: 10.3390/cancers13081775.

GUERRA, M.; LUNA, T.; SOUSA, A. et al. Local and system production of proinflammatory chemokines in the pathogenesis of HAM/TSP. Cellular Immunology. 2018; 334:70-77. doi: 10.1016/j.cellimm.2018.09.009.

HIRANO, T. IL-6 in inflammation, autoimmunity and cancer. International Immunology. 2020; 33(3):127-148. doi: 10.1093/intimm/dxaa078.

IULIANO, M.; MANGINO, G.; CHIANTORE, M. V. et al. Virus-Induced Tumorigenesis and IFN System. Biology. 2021; 1-21. doi: https://doi.org/10.3390/biology10100994.

KANNAGI, M.; HASEGAWA, A.; NAGANO, Y. et al. Impact of host immunity on HTLV-1 pathogenesis: potential of Tax-targeted immunotherapy against ATL. Retrovirology. 2019; 1-14. doi: https://doi.org/10.1186/s12977-019-0484-z.

KATAOKA, K.; NAGATA, Y.; OGAWA, S. et al. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nature genetics. 2015; 47(11):1304-1315. doi: 10.1038/ng.3415.

KE, H & YOO, D. The viral innate immune antagonism and an alternative vaccine design for PRRs virus. Veterinary Microbiology. 2017; 209:75-89. doi: 10.1016/j.vetmic.2017.03.014.

KELS, M. J. T.; NG, E.; RUMAIH, Z. A. et al. TNF deficiency dysregulates inflammatory cytokine production, leading to lung pathology and death during respiratory poxvirus infection. PNAS. 2020; 117(27):15935-15946. doi: 10.1073/pnas.2004615117.

KINPARA, S.; KIJIYAMA, M.; TAKAMORI, A. et al. Interferon-α (IFN-α) suppresses HTLV-1 gene expression and cell cycling, while IFN-α combined with zidovudin induces p53 signaling and apoptosis in HTLV-1-infected cells. Retrovirology. 2013; 10(52):1-15. doi: 10.1186/1742-4690-10-52.

KLEINER, G.; MARCUZZI, A.; ZANIN, V. et al. Cytokine levels in the serum of healthy subjects. Mediators of inflammation. 2013; 2013:1-6. doi: 10.1155/2013/434010.

LULA, L.; KEITELMAN, I. A.; SABBIONE, F. et al. Autophagy Mediates Interleukin-1β Secretion in Human Neutrophils. Frontiers in immunology. 2018; 9(269):1-14. doi: 10.3389/fimmu.2018.00269.

LUNA, T.; SANTOS, S. B.; NASCIMENTO, M. Effect of TNF-α production inhibition on the production of pro-inflammatory cytokines by peripheral blood mononuclear cells from HTLV-1-infected individuals. Brazilian Journal of Medical and Biological Research. 2011; 44(11):1134-1140. doi: 10.1590/s0100-879x2011007500140.

MALIK, A & KANNEGANTI, T. Function and Regulation of IL-1α in inflammatory diseases and cancer. Immunological Reviews. 2018; 124(1):124-137. doi: 10.1111/imr.12615.

MARCOVECCHIO, P. M.; THOMAS, G.; SALEK-ARDAKAMI, S. CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer. Journal for ImmunoTherapy of Cancer. 2021; 9(2):1-7. doi: 10.1136/jitc-2020-002045.

MATSUBARA, Y.; HORI, T.; MORITA, R. et al. Phenotypic and functional relationship between adult T-cell leukemia cells and regulatory T cells. Leukemia. 2005; 19(3):482-483. doi: 10.1038/sj.leu.2403628.

MERCOGLIANO, M. F.; BRUNI, S.; MAURO, F. et al. Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy. Cancers. 2021; 13(3):1-33. doi: 10.3390/cancers13030564.

MUSELLA, M.; GALASSI, C.; MANDUCA, N. et al. The Yin and Yang of Type I IFNs in Cancer Promotion and Immune Activation. Biology. 2021; 10(9):1-28. doi: 10.3390/biology10090856.

NAKAYAMA, Y.; ISHIKAWA, C.; TAMAKI, K. et al. Interleukin-1 alpha produced by human T-cell leukaemia virus type I-infected T cells induces intercellular adhesion molecule-1 expression on lung epithelial cells. Journal of Medical Microbiology. 2011; 1750-1761. doi: 10.1099/jmm.0.033456-0.

NAKAYAMA, Y.; YAMAZATO, Y.; TAMAYOSE, M. et al. Increased Expression of HBZ and Foxp3 mRNA in Bronchoalveolar Lavage Cells Taken from Human T-lymphotropic Virus Type 1-associated Lung Disorder Patients. Internal Medicine. 2013; 2599-2609. doi: 10.2169/internalmedicine.52.0845.

NOZUMA, S & JACOBSON, S. Neuroimmunology of Human T-Lymphotropic Virus Type 1-associated Myelopathy/Tropical Spastic Paraparesis. Frontiers in Microbiology. 2019; 10:1-11. doi: 10.3389/fmicb.2019.00885.

OKAMURA, T.; KATAYAMA, T.; OBINATA, C. et al. Neuronal injury induces microglial production of macrophage inflammatory protein-1α in rat corticostriatal slice cultures. Journal of Neuroscience Research. 2012. 90(11):2127-2133. doi: https://doi.org/10.1002/jnr.23105.

ORZALLI, M. H.; SMITH, A.; JURADO, K. A. et al. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Molecular Cell. 2018; 71(5):1-37. doi: 10.1016/j.molcel.2018.07.009.

PELISCH, N.; ALMANZA, J. R.; STEHLIK, K. E. et al. CCL3 contributes to secondary damage after spinal cord injury. Journal of Neuroinflammation. 2020; 17(362):1-16. doi: 10.1186/s12974-020-02037-3.

POL, J. G.; CAUDANA, P.; PAILLET, J. et al. Effects of interleukin-2 in immunostimulation and immunosuppression. Journal of Experimental Medicine. 2019; 2071(1):1-15. doi: 10.1084/jem.20191247.

ROJAS, J. M.; AVIA, M.; MARTÍN, V. et al. IL-10: A Multifunctional Cytokine in Viral Infections. Journal of Immunology Research. 2017; 1-14. doi: 10.1115/2017/6104054.

SAITO, M.; BANGHAM, C. R. M. Immunopathogenesis of Human T-Cell Leukemia Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis: Recent Perspctives. Leukemia Research and Treatment. 2012; 2012:1-12. doi: 10.1155/2012/259045.

SARAIVA, M.; VIEIRA, P.; O’GARRA, A. Biology and therapeutic potential of interleukin-10. Journal of Experimental Medicine. 2019; 271(1):1-19. doi: https://doi.org/10.1084/jem.20190418.

SATO, T.; REILLY-COLER, A.; UTSONOMIYA, A. et al. CSF CXCL10, CXCL9, and Neopterin as a Candidate Prognostic Biomarkers for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. Plos Neglected Tropical Diseases. 2013; 7(10):1-13. doi: 10.1371/journal.pntd.0002479.

SAWADA, L.; NAGANO, Y.; HASEGAWA, A. et al. IL-10-mediated signals act as a switch for lymphoproliferation in Human T-Cell leukemia virus type-1 infection by activating the STAT3 and IRF4 pathways. Plos Pathogens. 2017; 13(3):1-23. doi: 10.1371/journal.ppat.1006597.

STARLING, A. L. B.; ALVES, J. G. CDR.; PERUHYPE-MAGALHÃES, V. et al. Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity. Biomarkers. 2015; 1-12. doi: http://dx.doi.org/10.3109/1354750X.2015.1094141.

TANAKA, T.; NARAZAKI, M.; KISHIMOTO, T. IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology. 2014; 6(10):1-16. doi: 10.1101/cshperspect.a016295.

TANAKA, T.; NARAZAKI, M.; KISHIMOTO, T. Interleukin (IL-6) Immunotherapy. Cold Spring Harbor Perspectives in Biology. 2018; 10(8):1-15. doi: 10.1101/cshperspect.a028456.

TAROKHIAN, H.; RAHIMI, H.; MOSAVAT, A. et al. HTLV-1-host interactions on the development of adult T cell leukemia/lymphoma: virus and host gene expression. BMC Cancer. 2018; 18(1287):1-12. doi: https://doi.org/10.1186/s12885-018-5209-5.

TOKUNAGA, R.; ZHANG, W.; NASEEM, M. et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - a target for novel cancer therapy. Cancer Treat. Rev. 2018; 63:40-47. doi: 10.1016/j.ctrv.2017.11.007.

TRIFUNOVIC, J.; MILLER, L.; DEBELJACK, Z. et al. Patologic patterns of interleukin 10 expression - A review. Biochemia Medica. 2015; 25(1):36-48. doi: 10.11613/BM.2015.004.

YAMANO, Y.; ARAYA, N.; SATO, T. et al. Abnormally high levels of virus-infected IFN-gamma+CCR4+CD4+CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. Plos One. 2009; 4(8):1-14. doi: 10.1371/journal.pone.0006517.

ZARGARI, R.; MAHDIFAR, M.; MOHAMMADI, A. et al. The Role of Chemokines in the Pathogenesis of HTLV-1. Frontiers in Microbiology. 2020; 11(421):1-16. doi: 10.3389/fmicb.2020.00421.

ZHANG, Y.; YU, X.; LIN, D. et al. Propiece IL-1α facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-kβ and SP1. Oncotarget. 2017; 8(9):15677-15688. doi: 10.18632/oncotarget.14934.

Published

2022-07-06

Issue

Section

Original Papers