Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

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art_QUARESMA_Immunohistochemical_Characterization_of_M1_M2_and_M4_Macrophages_2023.PDF (2.43 MB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
QUARESMA, Tatiane Costa
VALENTIM, Livia de Aguiar
SOUSA, Jorge Rodrigues de
AARAO, Tinara Leila de Souza
FUZII, Hellen Thais
SOUZA, Juarez de
Citação
PATHOGENS, v.12, n.10, article ID 1225, 14p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Mycobacterium leprae is the etiological agent of leprosy. Macrophages (M phi s) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of M phi subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-na & iuml;ve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Par & aacute;, Bel & eacute;m, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-alpha) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-beta, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-alpha e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 +/- 1.3, p < 0.0001), Borderline (1.6 +/- 0.4, p < 0.0001), and tuberculoid (TT) (12.5 +/- 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 +/- 2.3, p < 0.0001), Borderline (1.3 +/- 0.2, p < 0.0001), and TT (3.2 +/- 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 +/- 1.7, p < 0.0001), Borderline (1.2 +/- 0.2, p < 0.0001), and TT (2.6 +/- 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 x TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 M phi s constituted the predominant M phi subpopulation in the TT and Borderline forms of leprosy, whereas the M2 M phi s showed increased immunoexpression and M4 was the predominant M phi phenotype in VV leprosy. These results confirm the relationship of the M phi profile with chronic pathological processes of the inflammatory response in leprosy.
Palavras-chave
leprosy, macrophages, immunohistochemistry, immunology
URI
https://observatorio.fm.usp.br/handle/OPI/58034
Referências
  1. Algood HMS, 2006, CLIN MICROBIOL REV, V19, P597, DOI 10.1128/CMR.00006-06
  2. Ambrosio AR, 2005, PARASITE IMMUNOL, V27, P333, DOI 10.1111/j.1365-3024.2005.00782.x
  3. Asim M, 2010, J BIOL CHEM, V285, P20343, DOI 10.1074/jbc.M110.116988
  4. Biagioli M, 2017, J IMMUNOL, V199, P718, DOI 10.4049/jimmunol.1700183
  5. Bobosha K, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002773
  6. Borlace GN, 2011, GUT PATHOG, V3, DOI 10.1186/1757-4749-3-3
  7. Boyle JJ, 2011, ARTERIOSCL THROM VAS, V31, P2685, DOI 10.1161/ATVBAHA.111.225813
  8. BRANDONISIO O, 1994, FEMS IMMUNOL MED MIC, V8, P57, DOI 10.1111/j.1574-695X.1994.tb00425.x
  9. Brizzi MF, 2012, CURR OPIN CELL BIOL, V24, P645, DOI 10.1016/j.ceb.2012.07.001
  10. Cardoso CC, 2011, FUTURE MICROBIOL, V6, P533, DOI [10.2217/FMB.11.39, 10.2217/fmb.11.39]
  11. Cervantes JL, 2019, TUBERCULOSIS, V116, pS131, DOI 10.1016/j.tube.2019.04.021
  12. Chiu YH, 2016, J CELL PHYSIOL, V231, P2402, DOI 10.1002/jcp.25389
  13. Cunha LD, 2018, CELL, V175, P429, DOI 10.1016/j.cell.2018.08.061
  14. Dalby E, 2020, J IMMUNOL, V205, P102, DOI 10.4049/jimmunol.1901382
  15. Fonseca ABD, 2017, INFECT DIS POVERTY, V6, DOI 10.1186/s40249-016-0229-3
  16. de Sousa JR, 2019, INFECT DRUG RESIST, V12, P2589, DOI 10.2147/IDR.S208576
  17. de Sousa JR, 2018, BMC INFECT DIS, V18, DOI 10.1186/s12879-018-3478-x
  18. de Sousa JR, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.01635
  19. de Sousa JR, 2016, ACTA TROP, V157, P108, DOI 10.1016/j.actatropica.2016.01.008
  20. Aarao TLD, 2014, MICROB PATHOGENESIS, V77, P66, DOI 10.1016/j.micpath.2014.10.005
  21. Sales JD, 2011, CLIN EXP IMMUNOL, V165, P251, DOI 10.1111/j.1365-2249.2011.04412.x
  22. Dejani NN, 2018, P NATL ACAD SCI USA, V115, pE8469, DOI 10.1073/pnas.1722016115
  23. do Carmo RF, 2021, INFECT GENET EVOL, V93, DOI 10.1016/j.meegid.2021.104945
  24. Elamin AA, 2012, J PATHOG, V2012, DOI 10.1155/2012/361374
  25. Erbel C, 2015, INNATE IMMUN-LONDON, V21, P255, DOI 10.1177/1753425914526461
  26. Forestier Claire-Lise, 2014, Front Cell Infect Microbiol, V4, P193, DOI 10.3389/fcimb.2014.00193
  27. Fulco TD, 2014, INFECT IMMUN, V82, P3968, DOI 10.1128/IAI.02194-14
  28. Gleissner CA, 2012, FRONT PHYSIOL, V3, DOI 10.3389/fphys.2012.00001
  29. Gleissner CA, 2010, J IMMUNOL, V184, P4810, DOI 10.4049/jimmunol.0901368
  30. Hirai KE, 2018, DIS MARKERS, V2018, DOI 10.1155/2018/7067961
  31. Huang J, 2014, NAT REV MICROBIOL, V12, P101, DOI 10.1038/nrmicro3160
  32. Jablonski KA, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0145342
  33. JACOBS JM, 1987, J NEUROL SCI, V79, P301, DOI 10.1016/0022-510X(87)90237-1
  34. Kaur G, 2017, FUTURE MICROBIOL, V12, P315, DOI 10.2217/fmb-2016-0173
  35. Kedzierska K, 2002, CURR MED CHEM, V9, P1893, DOI 10.2174/0929867023368935
  36. Khadilkar SV, 2021, J NEUROL SCI, V420, DOI 10.1016/j.jns.2020.117288
  37. Koller FL, 2012, LAB INVEST, V92, P1749, DOI 10.1038/labinvest.2012.141
  38. Lastória JC, 2014, AN BRAS DERMATOL, V89, P205, DOI 10.1590/abd1806-4841.20142450
  39. Liehl P, 2015, NAT REV MICROBIOL, V13, P589, DOI 10.1038/nrmicro3504
  40. Luo FL, 2016, WORLD J MICROB BIOT, V32, DOI 10.1007/s11274-015-1978-z
  41. Manicone AM, 2008, SEMIN CELL DEV BIOL, V19, P34, DOI 10.1016/j.semcdb.2007.07.003
  42. Marin A, 2021, CURR RES MICROB SCI, V2, DOI 10.1016/j.crmicr.2020.100015
  43. Matsumoto Y, 2005, HELICOBACTER, V10, P407, DOI 10.1111/j.1523-5378.2005.00349.x
  44. Mattos KA, 2011, CELL MICROBIOL, V13, P259, DOI 10.1111/j.1462-5822.2010.01533.x
  45. McMahan RS, 2016, J IMMUNOL, V197, P899, DOI 10.4049/jimmunol.1600502
  46. Mège JL, 2011, CURR OPIN INFECT DIS, V24, P230, DOI 10.1097/QCO.0b013e328344b73e
  47. Mendonça VA, 2008, AN BRAS DERMATOL, V83, P343, DOI 10.1590/S0365-05962008000400010
  48. Moraco AH, 2014, SEMIN IMMUNOL, V26, P497, DOI 10.1016/j.smim.2014.10.001
  49. Moura DF, 2012, EUR J IMMUNOL, V42, P2925, DOI 10.1002/eji.201142198
  50. Murray PJ, 2014, IMMUNITY, V41, P14, DOI 10.1016/j.immuni.2014.06.008
  51. Nakagawa M, 2021, CELLS-BASEL, V10, DOI 10.3390/cells10020257
  52. Nathan C, 2012, J CLIN INVEST, V122, P1189, DOI 10.1172/JCI62930
  53. Nikiforov N G, 2015, Patol Fiziol Eksp Ter, P128
  54. Novoselov VV, 2015, EXP MOL PATHOL, V99, P575, DOI 10.1016/j.yexmp.2015.09.014
  55. Okwor I, 2016, CELL IMMUNOL, V309, P32, DOI 10.1016/j.cellimm.2016.06.004
  56. Park AY, 2000, J IMMUNOL, V165, P896, DOI 10.4049/jimmunol.165.2.896
  57. Park AY, 2002, J IMMUNOL, V168, P5771, DOI 10.4049/jimmunol.168.11.5771
  58. Reibel F, 2015, MED MALADIES INFECT, V45, P383, DOI 10.1016/j.medmal.2015.09.002
  59. Ren YW, 2017, CURR ISSUES MOL BIOL, V21, P21, DOI 10.21775/cimb.021.021
  60. Rojas J, 2015, SCIENTIFICA, V2015, DOI 10.1155/2015/851252
  61. Salina A.C.G., 2020, Ph.D. Thesis
  62. Sanecka A, 2011, BMC IMMUNOL, V12, DOI 10.1186/1471-2172-12-57
  63. Santos D.O., 2007, Curr. Immunol. Rev, V3, P77, DOI 10.2174/157339507779802188
  64. Santos IKFD, 2001, INFECT IMMUN, V69, P5212, DOI 10.1128/IAI.69.8.5212-5215.2001
  65. Save MP, 2004, NEUROPATH APPL NEURO, V30, P635, DOI 10.1111/j.1365-2990.2004.00578.x
  66. Sawatani Y, 2008, INT IMMUNOL, V20, P1259, DOI 10.1093/intimm/dxn082
  67. SHETTY VP, 1988, J NEUROL SCI, V88, P115, DOI 10.1016/0022-510X(88)90210-9
  68. Sica A, 2015, CELL MOL LIFE SCI, V72, P4111, DOI 10.1007/s00018-015-1995-y
  69. Silva LM, 2018, INFECT DRUG RESIST, V11, P2231, DOI 10.2147/IDR.S172806
  70. Quaresma JAS, 2019, CLIN MICROBIOL REV, V32, DOI 10.1128/CMR.00034-18
  71. Quaresma JAS, 2012, MICROBES INFECT, V14, P696, DOI 10.1016/j.micinf.2012.02.010
  72. Quaresma JAS, 2010, MICROB PATHOGENESIS, V49, P135, DOI 10.1016/j.micpath.2010.05.003
  73. Solinas G, 2009, J LEUKOCYTE BIOL, V86, P1065, DOI 10.1189/jlb.0609385
  74. Stobie L, 2000, P NATL ACAD SCI USA, V97, P8427, DOI 10.1073/pnas.160197797
  75. Teixeira S.M., 2021, Ph.D. Thesis
  76. Teles RMB, 2013, SCIENCE, V339, P1448, DOI 10.1126/science.1233665
  77. Tomioka H, 2012, CLIN DEV IMMUNOL, DOI 10.1155/2012/635451
  78. Torchinsky MB, 2009, NATURE, V458, P78, DOI 10.1038/nature07781
  79. Van den Steen PE, 2003, BIOCHEM BIOPH RES CO, V310, P889, DOI 10.1016/j.bbrc.2003.09.098
  80. Vázquez S, 2021, ANIMALS-BASEL, V11, DOI 10.3390/ani11082301
  81. von Stebut E, 2003, J EXP MED, V198, P191, DOI 10.1084/jem.20030159
  82. von Stebut E, 1998, J EXP MED, V188, P1547, DOI 10.1084/jem.188.8.1547
  83. Woods JA, 2000, IMMUNOL CELL BIOL, V78, P545, DOI 10.1046/j.1440-1711.2000.00960.x
  84. Zeng XX, 2015, EUR REV MED PHARMACO, V19, P4353

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - LIM/06
Artigos e Materiais de Revistas Científicas - ODS/03