{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:11:16Z","timestamp":1790295076126,"version":"4.1.0"},"reference-count":38,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,8]]},"abstract":"<jats:p>Cutaneous leishmaniasis (CL), characterized by an ulcerated lesion, is the most common clinical form of human leishmaniasis. Before the ulcer develops, patients infected with <jats:italic>Leishmania<\/jats:italic> (<jats:italic>Viannia<\/jats:italic>) <jats:italic>braziliensis<\/jats:italic> 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. <jats:italic>Leishmania braziliensis<\/jats:italic> amastigotes, CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>, CD20<jats:sup>+<\/jats:sup>, and CD68<jats:sup>+<\/jats:sup> 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 <jats:italic>L. braziliensis<\/jats:italic>\u2013induced lesions.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0539","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T01:50:28Z","timestamp":1485222628000},"page":"645-652","source":"Crossref","is-referenced-by-count":36,"title":["Characterization of the Histopathologic Features in Patients in the Early and Late Phases of Cutaneous Leishmaniasis"],"prefix":"10.4269","volume":"96","author":[{"given":"Ma\u00edra G.","family":"Saldanha","sequence":"first","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto L.","family":"Machado","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Imunologia, Complexo Hospitalar Universit\u00e1rio Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas P.","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil."},{"name":"Servi\u00e7o de Imunologia, Complexo Hospitalar Universit\u00e1rio Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar M.","family":"de Carvalho Filho","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil."},{"name":"Servi\u00e7o de Imunologia, Complexo Hospitalar Universit\u00e1rio Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio","family":"Arruda","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"ref1","series-title":"Clin Infect Dis","first-page":"E69","article-title":"Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer","volume":"34","author":"Machado","year":"2002"},{"key":"ref2","series-title":"Am J Trop Med Hyg","first-page":"574","article-title":"Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil","volume":"80","author":"Unger","year":"2009"},{"key":"ref3","series-title":"J Infect Dis","first-page":"1288","article-title":"Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species","volume":"209","author":"Novais","year":"2014"},{"key":"ref4","series-title":"J Invest Dermatol","first-page":"1533","article-title":"CD8+Granzyme B+ mediated tissue injury versus CD4+IFNg+ mediated parasite killing in human cutaneous leishmaniasis","volume":"133","author":"Santos","year":"2013"},{"key":"ref5","series-title":"Infect Immun","first-page":"898","article-title":"Protective and pathological functions of CD8+ T cells in Leishmania braziliensis infection","volume":"83","author":"Cardoso","year":"2015"},{"key":"ref6","series-title":"PLoS Pathog","article-title":"Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis","volume":"9","author":"Novais","year":"2013"},{"key":"ref7","series-title":"Parasite Immunol","first-page":"551","article-title":"Tissue damage and immunity in cutaneous leishmaniasis","volume":"34","author":"Nylen","year":"2012"},{"key":"ref8","series-title":"Mem Inst Oswaldo Cruz","first-page":"202","article-title":"Comparative analysis of the tissue inflammatory response in human cutaneous and disseminated leishmaniasis","volume":"109","author":"Dantas","year":"2014"},{"key":"ref9","series-title":"Infect Immun","first-page":"6734","article-title":"Up regulation of Th1-type responses in mucosal leshmaniasis patients","volume":"70","author":"Bacellar","year":"2012"},{"key":"ref10","series-title":"Clin Exp Immunol","first-page":"59","article-title":"Intralesional plasma cell and serological responses in human cutaneous leishmaniasis","volume":"47","author":"Moriearty","year":"1982"},{"key":"ref11","series-title":"Mem Inst Oswaldo Cruz","first-page":"51","article-title":"Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis","volume":"86","author":"Bittencourt","year":"1991"},{"key":"ref12","series-title":"Br J Dermatol","first-page":"537","article-title":"Flow cytometric analysis of cellular infiltrate from American tegumentary leishmaniasis lesions","volume":"153","author":"Da-Cruz","year":"2005"},{"key":"ref13","series-title":"PLoS Negl Trop Dis","first-page":"e1947","article-title":"IFN-\u03b3 production to Leishmania antigen supplements the Leishmania skin test in identifying exposure to L. braziliensis infection","volume":"6","author":"Schnorr","year":"2012"},{"key":"ref14","series-title":"J Infect Dis","first-page":"274","article-title":"Intermediate monocytes contribute to pathologic immune response and L. braziliensis infections","volume":"211","author":"Passos","year":"2015"},{"key":"ref15","series-title":"J Clin Microbiol","first-page":"3892","article-title":"Serial quantitative PCR assay for detection, species discrimination, and quantification of Leishmania spp. in human samples","volume":"49","author":"Weirather","year":"2011"},{"key":"ref16","series-title":"Mem Inst Oswaldo Cruz","first-page":"987","article-title":"Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients","volume":"96","author":"Schubach","year":"2001"},{"key":"ref17","series-title":"Mem Inst Oswaldo Cruz","first-page":"239","article-title":"Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review","volume":"99","author":"Silveira","year":"2004"},{"key":"ref18","series-title":"Arch Pathol Lab Med","first-page":"235","article-title":"Comparison of conventional, molecular, and immunohistochemical methods in diagnosis of typical and atypical cutaneous leishmaniasis","volume":"138","author":"Shirian","year":"2014"},{"key":"ref19","series-title":"Hum Immunol","first-page":"1220","article-title":"Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis","volume":"71","author":"Campanelli","year":"2010"},{"key":"ref20","series-title":"BMC Infect","first-page":"75","article-title":"Macrophages participate in host protection and the disease pathology associated with Leishmania braziliensis infection","volume":"12","author":"Giudice","year":"2012"},{"key":"ref21","series-title":"PLoS Negl Trop Dis","first-page":"e1866","article-title":"Human macrophage response to L. (Viannia) panamensis: microarray evidence for an early inflammatory response","volume":"6","author":"Ramirez","year":"2012"},{"key":"ref22","series-title":"Immunol Lett","first-page":"226","article-title":"Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis","volume":"101","author":"Antonelli","year":"2005"},{"key":"ref23","series-title":"Rev Soc Bras Med Trop","first-page":"728","article-title":"CD8+ T cells in situ in different clinical forms of human cutaneous leishmaniasis","volume":"46","author":"Dantas","year":"2013"},{"key":"ref24","series-title":"Clin Exp Immunol","first-page":"338","article-title":"CD4+ T cells defined by their V\u03b2 T cell receptor expression are associated with immunoregulatory profiles and lesion size in human leishmaniasis","volume":"165","author":"Keesen","year":"2011"},{"key":"ref25","series-title":"Plos Pathogen","first-page":"e1003504","article-title":"Cytotoxic T cells mediates pathology and metastasis in cutaneous leishmaniasis","volume":"9","author":"Novais","year":"2013"},{"key":"ref26","series-title":"Parasite Immunol","first-page":"432","article-title":"Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis","volume":"31","author":"Faria","year":"2009"},{"key":"ref27","series-title":"Mem Inst Oswaldo Cruz","first-page":"979","article-title":"B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniasis","volume":"97","author":"Vieira","year":"2002"},{"key":"ref28","series-title":"Am J Trop Med Hyg","first-page":"854","article-title":"Cellular analysis of cutaneous leishmaniasis lymphadenopathy: insights into the early phases of human disease","volume":"77","author":"Bomfim","year":"2007"},{"key":"ref29","series-title":"An Bras Dermatol","first-page":"709","article-title":"Immunohistochemical profile of HIF-1\u03b1, VEGF-A, VEGFR2 and MMP9 proteins in tegumentary leishmaniasis","volume":"87","author":"Fraga","year":"2012"},{"key":"ref30","series-title":"Am J Trop Med Hyg","first-page":"743","article-title":"American cutaneous leishmaniasis: in situ characterization of the cellular immune response with time","volume":"50","author":"Lima","year":"1994"},{"key":"ref31","series-title":"An Bras Dermatol","first-page":"52","article-title":"American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters","volume":"89","author":"Martins","year":"2014"},{"key":"ref32","series-title":"Front Immunol","first-page":"145","article-title":"The immunobiology of Leishmania braziliensis infection","volume":"3","author":"Oliveira","year":"2012"},{"key":"ref33","series-title":"Acta Trop","first-page":"160","article-title":"MMP-9 activity is induced by Leishmania braziliensis infection and correlates with mucosal leishmaniasis","volume":"119","author":"Maretti-Mira","year":"2011"},{"key":"ref34","series-title":"PLoS Negl Trop Dis","first-page":"e3282","article-title":"Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous leishmaniasis","volume":"8","author":"Campos","year":"2014"},{"key":"ref35","series-title":"J Leukoc Biol","first-page":"584","article-title":"The CD14+ CD16+ blood monocytes: their role in infection and inflammation","volume":"81","author":"Ziegler-Heitbrock","year":"2007"},{"key":"ref36","series-title":"Science","first-page":"1357","article-title":"Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis","volume":"343","author":"Newton","year":"2014"},{"key":"ref37","series-title":"Parasite Immunol","first-page":"65","article-title":"Immunoregulatory profile of monocytes from cutaneous leishmaniasis patients and association with lesion size","volume":"35","author":"Vieira","year":"2013"},{"key":"ref38","series-title":"PLoS One","first-page":"e0148084","article-title":"The role of nitric oxide and reactive oxygen species in the killing of Leishmania braziliensis by monocytes from patients with cutaneous leishmaniasis","volume":"11","author":"Carneiro","year":"2016"}],"container-title":["The American Society of Tropical Medicine and 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