{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:44:03Z","timestamp":1778625843270,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T00:00:00Z","timestamp":1414454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous leishmaniasis is an infection that has spread to non\u2010endemic regions, stimulating recent interest for the enhanced understanding of this disease. Downregulation of the CD1a receptor on Langerhans cells has been described in various cutaneous infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>In this study, the immune response across different Ridley patterns and parasitic indices is outlined in a case series of cutaneous leishmaniasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin punch biopsies from the interface of normal and lesional cutaneous leishmaniasis were collected from 33 patients with molecularly confirmed <jats:italic>Leishmania tropica or L. major<\/jats:italic> infection. Ridley patterns (2\u20135) were assessed for various clinicopathological features including age, gender, disease duration, parasitic index and constituents of the inflammatory infiltrate. CD1a, CD68, CD3, CD4, CD8, CD20 and CD138 stains were performed on normal skin tissue, cutaneous leishmaniasis biopsies and cytospin\/cell block cytology preparations of cultured leishmania promastigotes. CD1a was quantified per mm\u00b2 in the epidermis and dermis. The remaining stains were graded according to a 4\u2010tiered grading system [0 (0\u20134%); 1 (5\u201324%); 2 (25\u201349%); 3 (50\u201374%) and 4 (75\u2013100%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total CD1a expression significantly decreased (14\u2010fold) from parasitic indices (0\u20132) to (5\u20136); (\u03c1\u00a0&lt;\u00a00.001). CD1a expression in the epidermis was at least 5\u2010fold lower than normal skin (58 vs. 400 cells\/mm\u00b2), inversely correlating with the parasitic index. There was an increase in dermal CD1a Langerhans cells (33 vs. 0 cells\/mm\u00b2 in the dermis). CD1a and CD68 staining of amastigotes was strong and diffuse, whereas promastigotes were negative. The major inflammatory infiltrate, in all Ridley patterns, consisted of macrophages and double\u2010negative CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>\u2212<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup> T lymphocytes. The double\u2010negative CD3 T cells formed a ring around the parasitic laden macrophages. Apart from CD1a, there was no significant difference in inflammatory markers between the various Ridley patterns and parasitic indices. Disease duration did not correlate with Ridley pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The significant decrease in CD1a expression is postulated by two mechanisms; either via direct CD1a receptor uptake by leishmania amastigotes and\/or negative feedback inhibition of CD1a Langerhans cells by double\u2010negative CD3 T\u2010regulatory cells. Modulation of the immune microenvironment in cutaneous leishmaniasis represents a potential therapeutic and prophylactic target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.12781","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T03:11:24Z","timestamp":1414552284000},"page":"1170-1179","source":"Crossref","is-referenced-by-count":25,"title":["The immune microenvironment in cutaneous leishmaniasis"],"prefix":"10.1111","volume":"29","author":[{"given":"M.N.","family":"Jabbour","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Charafeddine","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Simaan","sequence":"additional","affiliation":[{"name":"Department of Biology University of Balamand Tripoli Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Karam","sequence":"additional","affiliation":[{"name":"Department of Biology University of Balamand Tripoli Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Khalifeh","sequence":"additional","affiliation":[{"name":"Children's Cancer Center Lebanon American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Khalifeh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(96)80121-6"},{"key":"e_1_2_7_3_1","first-page":"253","article-title":"Current status of cutaneous leishmaniasis in Aleppo, Syrian Arab Republic","volume":"75","author":"Douba M","year":"1997","journal-title":"Bull World Health Organ"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70492-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1276-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2008.02063.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1407.071589"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2007.01998.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4081\/gh.2009.214"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00416-09"},{"issue":"37","key":"e_1_2_7_11_1","first-page":"179","article-title":"Is leishmaniasis becoming endemic in Germany?","volume":"293","author":"Naucke TJ","year":"2004","journal-title":"Int J Med Microbiol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-008-1052-y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2807\/ese.15.10.19505-en"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04266.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113292"},{"key":"e_1_2_7_16_1","first-page":"95","article-title":"The Langerhans cell","volume":"3","author":"Rowden G","year":"1981","journal-title":"Crit Rev Immunol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1983.5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2930-9_98"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230730"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01611181"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250310"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-9966-8_89"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12525745"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12261453"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.51.3.838-843.1986"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12277399"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1988.tb02453.x"},{"key":"e_1_2_7_28_1","first-page":"72","article-title":"The vitamin D3 analog calcipotriol suppresses the number and antigen\u2010presenting function of Langerhans cells in normal human skin","volume":"1","author":"Dam TN","year":"1996","journal-title":"J Investig Dermatol Symp Proc"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02359.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2012.01890.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(80)90069-3"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711410109"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.12.4451"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0307187"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2007.00970.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2012.01923.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2005.03.035"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102318"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.212"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00890-06"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2012.04611.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni832"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.9.5624"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.4.1947"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020029"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:35:1:163"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01152"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141428"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2005.04.016"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1996.55.365"},{"key":"e_1_2_7_51_1","first-page":"371","article-title":"Immunophenotypic pattern and cytokine profiles of dry type cutaneous leishmaniasis","volume":"12","author":"Meymandi S","year":"2009","journal-title":"Arch Iran Med"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100367"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.10.004"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2002.110104.x"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09573.x"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2013.07.021"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040484"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1592"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3800::AID-IMMU3800>3.0.CO;2-0"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.3171"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3719-3726.1999"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2253"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.5811"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4624-4630.2000"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016791108"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4100"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdv.12781","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdv.12781","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.12781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T11:50:57Z","timestamp":1695556257000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.12781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,28]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/jdv.12781"],"URL":"https:\/\/doi.org\/10.1111\/jdv.12781","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,28]]}}}