Volume 96, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Cutaneous leishmaniasis (CL), characterized by an ulcerated lesion, is the most common clinical form of human leishmaniasis. Before the ulcer develops, patients infected with () present a small papule at the site of the sandfly bite, referred to as early cutaneous leishmaniasis (E-CL). Two to four weeks later the typical ulcer develops, which is considered here as late CL (L-CL). Although there is a great deal known about T-cell responses in patients with L-CL, there is little information about the in situ inflammatory response in E-CL. Histological sections of skin biopsies from 15 E-CL and 28 L-CL patients were stained by hematoxilin and eosin to measure the area infiltrated by cells, as well as tissue necrosis. amastigotes, CD4, CD8, CD20, and CD68 cells were identified and quantified by immunohistochemistry. The number of amastigotes in E-CL was higher than in L-CL, and the inflammation area was larger in classical ulcers than in E-CL. There was no relationship between the number of parasites and magnitude of the inflammation area, or with the lesion size. However, there was a direct correlation between the number of macrophages and the lesion size in E-CL, and between the number of macrophages and necrotic area throughout the course of the disease. These positive correlations suggest that macrophages are directly involved in the pathology of –induced lesions.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Machado P, Araújo C, Da Silva AT, Almeida RP, D'Oliveira A, Jr Bittencourt A, Carvalho EM, , 2002. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis 34: E69E73.[Crossref] [Google Scholar]
  2. Unger A, O'Neal S, Machado PR, Guimarães LH, Morgan DJ, Schriefer A, Bacellar O, Glesby MJ, Carvalho EM, , 2009. Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. Am J Trop Med Hyg 80: 574579. [Google Scholar]
  3. Novais FO, Nguyen BT, Beiting DP, Carvalho LP, Glennie ND, Passos S, Carvalho EM, Scott P, , 2014. Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species. J Infect Dis 209: 12881296.[Crossref] [Google Scholar]
  4. Santos C d S, Boaventura V, Cardoso CR, Tavares N, Lordelo MJ, Noronha A, Costa J, Borges VM, Oliveira CI, Weyenbergh JV, Barral A, Barral-Netto M, Brodskyn CI, , 2013. CD8+Granzyme B+ mediated tissue injury versus CD4+IFNg+ mediated parasite killing in human cutaneous leishmaniasis. J Invest Dermatol 133: 15331540.[Crossref] [Google Scholar]
  5. Cardoso TM, Machado A, Costa DL, Carvalho LP, Queiroz A, Machado P, Scott P, Carvalho EM, Bacellar O, , 2015. Protective and pathological functions of CD8+ T cells in Leishmania braziliensis infection. Infect Immun 83: 898906.[Crossref] [Google Scholar]
  6. Novais FO, Carvalho LP, Graff JW, Beiting DP, Ruthel G, Roos DS, Betts MR, Goldschmidt MH, Wilson ME, Oliveira CI, Scott P, , 2013. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. PLoS Pathog 9: e1003504.[Crossref] [Google Scholar]
  7. Nylen S, Eidsmo L, , 2012. Tissue damage and immunity in cutaneous leishmaniasis. Parasite Immunol 34: 551561.[Crossref] [Google Scholar]
  8. Dantas ML, Oliveira JM, Carvalho L, Passos ST, Queiroz A, Guimarães LH, Machado P, Carvalho E, Arruda S, , 2014. Comparative analysis of the tissue inflammatory response in human cutaneous and disseminated leishmaniasis. Mem Inst Oswaldo Cruz 109: 202209.[Crossref] [Google Scholar]
  9. Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM, , 2012. Up regulation of Th1-type responses in mucosal leshmaniasis patients. Infect Immun 70: 67346740.[Crossref] [Google Scholar]
  10. Moriearty PL, Grimaldi G, Jr Galvão-Castro B, de Oliveira Neto MP, Marzochi MC, , 1982. Intralesional plasma cell and serological responses in human cutaneous leishmaniasis. Clin Exp Immunol 47: 5964. [Google Scholar]
  11. Bittencourt AL, Barral A, , 1991. Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis. Mem Inst Oswaldo Cruz 86: 5156.[Crossref] [Google Scholar]
  12. Da-Cruz AM, Bertho AL, Oliveira-Neto MP, Coutinho SG, , 2005. Flow cytometric analysis of cellular infiltrate from American tegumentary leishmaniasis lesions. Br J Dermatol 153: 537543.[Crossref] [Google Scholar]
  13. Schnorr D, Muniz AC, Passos S, Guimaraes LH, Lago EL, Bacellar O, Glesby MJ, Carvalho EM, , 2012. IFN-γ production to Leishmania antigen supplements the Leishmania skin test in identifying exposure to L. braziliensis infection. PLoS Negl Trop Dis 6: e1947.[Crossref] [Google Scholar]
  14. Passos S, Carvalho LP, Costa RS, Campos TM, Novais F, Magalhães A, Machado PRL, Betting D, Moser D, Carvalho EM, Scott P, , 2015. Intermediate monocytes contribute to pathologic immune response and L. braziliensis infections. J Infect Dis 211: 274282.[Crossref] [Google Scholar]
  15. Weirather JL, Jeronimo SMB, Gautam S, Sundar S, Kang M, Kurtz MA, Haque R, Schriefer A, Talhari S, Carvalho EM, Donelson JE, Wilson ME, , 2011. Serial quantitative PCR assay for detection, species discrimination, and quantification of Leishmania spp. in human samples. J Clin Microbiol 49: 38923904.[Crossref] [Google Scholar]
  16. Schubach A, Cuzzi-Maya T, Oliveira AV, Sartori A, Oliveira-Neto MP, Mattos MS, Araújo ML, Souza WJS, Haddad F, Perez MA, Pacheco RS, Momen H, Coutinho SG, Marzochi MCA, Marzochi KBF, Costa SCG, , 2001. Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients. Mem Inst Oswaldo Cruz 96: 987996.[Crossref] [Google Scholar]
  17. Silveira FT, Lainson R, Corbett CEP, , 2004. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz 99: 239251.[Crossref] [Google Scholar]
  18. Shirian S, Oryan A, Hatam G-R, Panahi S, Daneshbod Y, , 2014. Comparison of conventional, molecular, and immunohistochemical methods in diagnosis of typical and atypical cutaneous leishmaniasis. Arch Pathol Lab Med 138: 235240.[Crossref] [Google Scholar]
  19. Campanelli AP, Brodskyn CI, Boaventura V, Silva C, Roselino AM, Costa J, Saldanha AC, de Freitas LA, de Oliveira CI, Barral-Netto M, Silva JS, Barral A, , 2010. Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis. Hum Immunol 71: 12201227.[Crossref] [Google Scholar]
  20. Giudice A, Vendrame C, Bezerra C, Carvalho LP, Delavechia T, Carvalho EM, Bacellar O, , 2012. Macrophages participate in host protection and the disease pathology associated with Leishmania braziliensis infection. BMC Infect 12: 75.[Crossref] [Google Scholar]
  21. Ramirez C, Diaz-Toro Y, Tellez J, Castilho TM, Rojas R, Ettinger NA, Tikhonova I, Alexander ND, Valderrama L, Hager J, Wilson ME, Lin A, Zhao H, Saravia NG, McMahon-Pratt D, , 2012. Human macrophage response to L. (Viannia) panamensis: microarray evidence for an early inflammatory response. PLoS Negl Trop Dis 6: e1866.[Crossref] [Google Scholar]
  22. Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Carvalho EM, Gollob KJ, , 2005. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis. Immunol Lett 101: 226230.[Crossref] [Google Scholar]
  23. Dantas ML, de Oliveira JC, Carvalho L, Passos ST, Queiroz A, Machado P, Carvalho E, Arruda S, , 2013. CD8+ T cells in situ in different clinical forms of human cutaneous leishmaniasis. Rev Soc Bras Med Trop 46: 728734.[Crossref] [Google Scholar]
  24. Keesen TSL, Antonelli LRV, Faria DR, Guimarães LH, Bacellar O, Carvalho EM, Dutra WO, Gollob KJ, , 2011. CD4+ T cells defined by their Vβ T cell receptor expression are associated with immunoregulatory profiles and lesion size in human leishmaniasis. Clin Exp Immunol 165: 338351.[Crossref] [Google Scholar]
  25. Novais FO, Carvalho LP, Graff JW, Beiting DP, Ruthel G, Roos DS, Betts MR, Goldschmidt MH, Wilson ME, Oliveira CI, Scott P, , 2013. Cytotoxic T cells mediates pathology and metastasis in cutaneous leishmaniasis. Plos Pathogen 9: e1003504.[Crossref] [Google Scholar]
  26. Faria DR, Souza PE, Duraes FV, Carvalho EM, Gollob KJ, Machado PR, Dutra WO, , 2009. Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis. Parasite Immunol 31: 432439.[Crossref] [Google Scholar]
  27. Vieira MG, Oliveira F, Arruda S, Bittencourt AL, Barbosa AA, Jr Barral-Netto M, Barral A, , 2002. B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniasis. Mem Inst Oswaldo Cruz 97: 979983.[Crossref] [Google Scholar]
  28. Bomfim G, Andrade BB, Santos S, Clarencio J, Barral-Netto M, Barral A, , 2007. Cellular analysis of cutaneous leishmaniasis lymphadenopathy: insights into the early phases of human disease. Am J Trop Med Hyg 77: 854859. [Google Scholar]
  29. Fraga CA, Oliveira MV, Alves LR, Viana AG, Sousa AA, Carvalho SF, de Paula AMB, Botelho ACC, Guimarães ALS, , 2012. Immunohistochemical profile of HIF-1α, VEGF-A, VEGFR2 and MMP9 proteins in tegumentary leishmaniasis. An Bras Dermatol 87: 709713.[Crossref] [Google Scholar]
  30. Lima HC, Vasconcelos AW, David JR, Lerner EA, , 1994. American cutaneous leishmaniasis: in situ characterization of the cellular immune response with time. Am J Trop Med Hyg 50: 743. [Google Scholar]
  31. Martins ALGP, Barreto JA, Lauris JRP, Martins ACGP, , 2014. American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters. An Bras Dermatol 89: 5258.[Crossref] [Google Scholar]
  32. Oliveira CI, Brodskyn CI, , 2012. The immunobiology of Leishmania braziliensis infection. Front Immunol 3: 145.[Crossref] [Google Scholar]
  33. Maretti-Mira AC, de Pinho Rodrigues KM, de Oliveira-Neto MP, Pirmez C, Craft N, , 2011. MMP-9 activity is induced by Leishmania braziliensis infection and correlates with mucosal leishmaniasis. Acta Trop 119: 160164.[Crossref] [Google Scholar]
  34. Campos TM, Passos ST, Novais FO, Beiting DP, Costa RS, Queiroz A, Mosser D, Scott P, Carvalho EM, Carvalho LP, , 2014. Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous leishmaniasis. PLoS Negl Trop Dis 8: e3282.[Crossref] [Google Scholar]
  35. Ziegler-Heitbrock L, , 2007. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 81: 584592.[Crossref] [Google Scholar]
  36. Newton K, Dugger DL, Wickliffe KE, Kapoor N, de Almagro MC, Vucic D, Komuves L, Ferrando RE, French DM, Webster J, Roose-Girma M, Warming S, Dixit VM, , 2014. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 343: 13571360.[Crossref] [Google Scholar]
  37. Vieira ÉL, Keesen TS, Machado PR, Guimarães LH, Carvalho EM, Dutra WO, Gollob KJ, , 2013. Immunoregulatory profile of monocytes from cutaneous leishmaniasis patients and association with lesion size. Parasite Immunol 35: 6572.[Crossref] [Google Scholar]
  38. Carneiro PP, Conceição J, Macedo M, Magalhães V, Carvalho EM, Bacellar O, , 2016. The role of nitric oxide and reactive oxygen species in the killing of Leishmania braziliensis by monocytes from patients with cutaneous leishmaniasis. PLoS One 11: e0148084.[Crossref] [Google Scholar]

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  • Received : 30 Jan 2016
  • Accepted : 11 Sep 2016
  • Published online : 23 Jan 2017

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