Impaired T-cell-dependent protection against Leishmania major infection in HIV-positive patients is associated with worsened disease outcome.

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.