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Title: The immune microenvironment in cutaneous leishmaniasis
Authors: Jabbour, M. N
Issa, G.
Charafeddine, K.
Simaan, Youssef
Karam, Marc 
Khalifeh, Hassan
Habib, R.
Khalifeh, Ibrahim
Affiliations: Department of Biology 
Issue Date: 2015
Part of: Journal of the european academy of dermatology and venereology
Volume: 29
Issue: 6
Start page: 1170
End page: 1179
Background Cutaneous leishmaniasis is an infection that has spread to non‐endemic 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. Objective In this study, the immune response across different Ridley patterns and parasitic indices is outlined in a case series of cutaneous leishmaniasis. Methods Skin punch biopsies from the interface of normal and lesional cutaneous leishmaniasis were collected from 33 patients with molecularly confirmed Leishmania tropica or L. major infection. Ridley patterns (2–5) 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 mm² in the epidermis and dermis. The remaining stains were graded according to a 4‐tiered grading system [0 (0–4%); 1 (5–24%); 2 (25–49%); 3 (50–74%) and 4 (75–100%). Results Total CD1a expression significantly decreased (14‐fold) from parasitic indices (0–2) to (5–6); (ρ < 0.001). CD1a expression in the epidermis was at least 5‐fold lower than normal skin (58 vs. 400 cells/mm²), inversely correlating with the parasitic index. There was an increase in dermal CD1a Langerhans cells (33 vs. 0 cells/mm² 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‐negative CD3+CD4−CD8− T lymphocytes. The double‐negative 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 pattern Conclusion 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‐negative CD3 T‐regulatory cells. Modulation of the immune microenvironment in cutaneous leishmaniasis represents a potential therapeutic and prophylactic target.
DOI: 10.1111/jdv.12781
Ezproxy URL: Link to full text
Type: Journal Article
Appears in Collections:Department of Biology

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