The pathogenesis of post kala-azar dermal leishmaniasis from the field to the molecule: does ultraviolet light (UVB) radiation play a role?
Post kala-azar dermal leishmaniasis (PKDL) is a dermatosis caused by persistence of Leishmania donovani parasites in the skin following apparently successful treatment of visceral leishmaniasis. The distribution of PKDL lesions in Sudanese patients often mirrors the clothing habits of those affected. It is most severe in or confined to the sun-exposed parts of the skin. It is well established that elimination of Leishmania parasites requires activation of parasitised macrophages by a Th1 immune response and that the latter is depressed by ultraviolet light (UVB). In this paper, we hypothesized that UVB light might be a key player in the pathogenesis of PKDL. This paper links observations made in the field with immunological data that are compatible with this hypothesis. We therefore investigated patients with PKDL immunologically for a possible role of UVB exposure in the pathogenesis of this condition. We marshal evidence that the changes in the tissues are compatible with the effects of UVB light and it is probable that UVB appears to be a key factor in the pathogenesis of PKDL. Immunopathologically the lesions were characterized by an influx of various inflammatory cells. The number of CD1a (Langerhans' cells) was decreased, they lost their dendrites, their HLA-DR and B7-1 expression was down regulated while B7-2 was expressed. Others have shown that Langerhans' cells with these features result from UVB exposure and that such cells are unable to present antigen to Th1 cells while retaining the capacity to present antigen to Th2 cells. Various cytokines known to be induced by UVB radiation could be demonstrated in PKDL lesions. Of these IL-10, TGF-beta, IL-12, IL-4 and TNF-alpha were found in different quantities. The Th-1 cytokine IFN-gamma was constantly present. The tissue origin of the Th-1 cells in PKDL is unknown. We believe that the antagonistic action of the different cytokines is the cause of the inflammation and chronicity of PKDL.
Ismail
A
A
Department of Clinical Pathology and Immunology, Faculty of Medicine, Institute of Endemic Diseases, University of Khartoum, Medical Sciences Campus, Sudan. aicmp@yahoo.com
Khalil
E A G
EA
Musa
A M
AM
El Hassan
I M
IM
Ibrahim
M E
ME
Theander
T G
TG
El Hassan
A M
AM
D016207:Cytokines / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000528:radiation effects; D007898:Leishmaniasis, Visceral / Q000209:etiology* / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology* / Q000528:radiation effects*; D012867:Skin / Q000276:immunology / Q000528:radiation effects; D012876:Skin Diseases, Parasitic / Q000209:etiology* / Q000276:immunology*; D013397:Sudan; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016207:Cytokines