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Epidermal compromise in American cutaneous leishmaniasis
G Cáceres-Dittmar1, M A Sánchez, O Oriol
1Instituto de Biomedicina, Universidad Central de Venezuela, Caracas.
The Journal of Investigative Dermatology
|November 1, 1992
Summary
The epidermis plays a crucial role in determining immune responses to American cutaneous leishmaniasis (ACL). Immune cell and cytokine expression in the skin varies significantly across ACL forms, impacting disease development.
Area of Science:
- Immunology
- Dermatology
- Parasitology
Background:
- American cutaneous leishmaniasis (ACL) presents with diverse immune responses, ranging from effective localized cutaneous leishmaniasis (LCL) to diffuse cutaneous leishmaniasis (DCL) with selective anergy, and muco-cutaneous leishmaniasis (MCL) with exacerbated cell-mediated immunity.
- The epidermis harbors key immune cells like Langerhans cells (LC) and expresses molecules crucial for immune regulation, such as HLA-DR and intercellular adhesion molecule-1 (ICAM-1).
Purpose of the Study:
- To investigate the role of the epidermis and its resident immune cells in modulating the distinct clinical manifestations of American cutaneous leishmaniasis (ACL).
- To correlate epidermal immune cell populations and molecular markers with different forms of ACL (LCL, DCL, MCL).
Main Methods:
- Analysis of epidermal immune cell populations (Langerhans cells - LC, dendritic epidermal T cells - DETC) and expression of HLA-DR, ICAM-1, and cytokine mRNA (IL-1 beta, IL-8, TNF alpha, TNF beta, INF gamma) in human ACL skin biopsies.
- Experimental reproduction of ACL in inbred mice to study the correlation between LC and DETC numbers and the impact of modulating these cells on disease development.
Main Results:
- LCL epidermis showed increased LC, universal HLA-DR, and patchy ICAM-1 expression, with detectable cytokine mRNA. DCL epidermis had fewer LC and undetectable ICAM-1, HLA-DR, and IL-1 beta mRNA. MCL lesions lacked LC but showed universal ICAM-1.
- In healthy mice, LC and DETC numbers were positively correlated. This correlation was absent in Leishmania mexicana-infected mice, indicating infection alters immune cell balance.
- Modulating LC and DETC cell densities affected the development of experimental leishmaniasis.
Conclusions:
- The epidermis is critical in determining the type of immune response mounted against Leishmania parasites in ACL.
- Distinct patterns of epidermal immune cell infiltration and molecular marker expression correlate with the clinical spectrum of ACL.
- Alterations in the balance of epidermal immune cells, such as LC and DETC, are implicated in the pathogenesis of leishmaniasis.