title: Interferon-gamma treatment induces granulomatous tissue reaction in a case of localized cutaneous leishmaniasis.
abstract: Leishmania spp. suppress macrophage activity as part of their interaction with the immune system. Interferon-gamma (IFNgamma), a cytokine that participates in the activation of macrophages and the killing of intercellular parasites, induces healing of leishmaniasis. We investigated a sequence of local and systemic inflammatory cell parameters after IFNgamma therapy in a patient with chronic, localized, cutaneous leishmaniasis caused by Leishmania donovani. Histology, immunohistochemistry, polymerase chain reaction (PCR) for L. donovani, and analysis of T-cell receptor gene fragments from skin lesions as well as peripheral blood phenotyping were performed before, during, and after IFNgamma therapy. During therapy, epithelioid cell granulomas developed with a high number of lesional human leukocyte antigen (HLA) DR+ macrophages, and HLA-DR expression on monocytes increased to high counts, indicating macrophage activation. Simultaneously, T-cell receptor-beta gene-specific PCR showed a peak at 243 base pairs, indicating clonal expansion of Leishmania-reactive T lymphocytes. After therapy, PCR detected minimal residual leishmanial DNA in healing lesions, suggesting the destruction of the parasites. In conclusion, IFNgamma therapy compensates for the parasite-dependent major histocompatibility complex class II downregulation and induces healing of chronic cutaneous leishmaniasis.
authors.affiliation: Department of Dermatology and Allergy, Charité, Humboldt-University Berlin, Berlin, Germany. norb.haas@charite.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Haas
authors.forename: Steffen
authors.initials: S
authors.lastname: Hauptmann
authors.forename: Dimitra
authors.initials: D
authors.lastname: Paralikoudi
authors.forename: Marcus
authors.initials: M
authors.lastname: Muche
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kolde
mesh_terms: D000328:Adult; D000818:Animals; D016054:DNA, Protozoan / Q000032:analysis; D019672:Genes, T-Cell Receptor / Q000235:genetics; D006099:Granuloma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000627:therapeutic use*; D007893:Leishmania donovani / Q000235:genetics / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000032:analysis
chemical_list: D016054:DNA, Protozoan; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma