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Impaired T‐cell‐dependent protection against Leishmania major infection in HIV‐positive patients is associated with worsened disease outcome
Authors:Omer Bébé Ngouateu  Karsten Weller  Konrad Bröhl  Pierre Kamtchouing  Albert Same‐Ekobo  Blaise Dondji  Marcus Maurer  Esther von Stebut
Institution:1. Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon;2. Laboratory of Leishmaniasis Research Project, Mokolo District Hospital, Mokolo, Cameroon;3. Department of Dermatology, University Medicine, Johannes Gutenberg‐University, Mainz, Germany;4. Department of Dermatology and Allergy, Charité – Universit?tsmedizin Berlin, Berlin, Germany;5. Laboratory of Parasitology, Yaoundé Teaching Hospital, Yaoundé, Cameroon;6. Department of Biological Sciences, Central Washington University, Ellensburg, WA, USA
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.
Keywords:antigen‐presenting cells  cutaneous leishmaniasis     HIV     human  T cells
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