Leishmania donovani and HIV co-infection in vitro: Identification and characterization of main molecular players

Abstract

The incidence of Leishmania/HIV co-infection is growing and few studies detail the cellular processes and macromolecules participating in co-infection. Thus, the goal of this study was to partially describe the Leishmania/HIV co-infection events by measuring molecular and functional parameters associated with both pathogens in vitro. MT-4 cells (human T-lymphocytes), primary monocytes, and peripheral blood mononuclear cells were exposed to HIV and/or Leishmania donovani. The cytopathic effects generated by the pathogens were observed through microscopy. Viral replication was assessed by monitoring p24 protein levels and parasitic proliferation/infectivity was determined using Giemsa staining. Changes in molecular markers were evaluated by ELISA and fluorescence assays. Our results showed that our system reassembles the main parameters previously described for Leishmania/HIV co-infection in patients in terms of potentiation of parasitic and viral replication/infectivity, amplification of syncytia induction, and alterations of cell viability. In addition, an amplification in NF-κB activation, changes in CXCR4/CCR5 surface expression, and a Th1→Th2 variation in cytokine/chemokine secretion were demonstrated. Altogether, this study could contribute to gain a deep understanding of the molecular events associated with Leishmania/HIV co-infection.