title: Impaired T-cell-dependent protection against Leishmania major infection in HIV-positive patients is associated with worsened disease outcome.
abstract: Cutaneous leishmaniasis (CL) patients coinfected with HIV are known to show a more severe, prolonged course of disease; the immunological basis is not known. We now assessed clinical features, sera and skin biopsies of HIV(+) and HIV(-) patients with CL to identify drivers of increased susceptibility to Leishmania. CL lesion numbers, surface, and healing duration were significantly increased in HIV(+) as compared to HIV(-) patients (2.5, 14 and >4-fold, respectively). Patients with HIV infection exhibited lower serum Leishmania-specific IgG levels and decreased IL-6 and IL-8. Most importantly, dramatically decreased numbers of CD4(+) T cells (approximately eightfold), but not CD8(+) cells, together with fewer CXCR3(+) Th1 cells, fewer Foxp3(+) effector/regulatory T cells, and reduced levels of IFN-γ expression were found in lesional skin. Our findings suggest that compromised CD4(+) T-cell responses may be responsible for worsened disease outcome leading to defects in parasite elimination in the absence of sufficient numbers of IFN-γ-producing Th1 cells.
authors: Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon; Laboratory of Leishmaniasis Research Project, Mokolo District Hospital, Mokolo, Cameroon; Department of Dermatology, University Medicine, Johannes Gutenberg-University, Mainz, Germany; Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: Omer Bébé
authors: OB
authors: Ngouateu
authors: Karsten
authors: K
authors: Weller
authors: Konrad
authors: K
authors: Bröhl
authors: Pierre
authors: P
authors: Kamtchouing
authors: Albert
authors: A
authors: Same-Ekobo
authors: Blaise
authors: B
authors: Dondji
authors: Marcus
authors: M
authors: Maurer
authors: Esther
authors: E
authors: von Stebut
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection / Q000276:immunology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D008297:Male; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D007371:Interferon-gamma
keywords: HIV; T cells; antigen-presenting cells; cutaneous leishmaniasis; human