In vivo characterization of two additional Leishmania donovani strains using the murine and hamster model

Abstract

Leishmania donovani is a protozoan parasite causing the neglected tropical disease visceral leishmaniasis. One difficulty to study the immunopathology upon L. donovani infection is the limited adaptability of the strains to experimental mammalian hosts. Our knowledge about L. donovani infections relies on a restricted number of East African strains (LV9, 1S). Isolated from patients in the 1960s, these strains were described extensively in mice and Syrian hamsters and have consequently become 'reference' laboratory strains. L. donovani strains from the Indian continent display distinct clinical features compared to East African strains. Some reports describing the in vivo immunopathology of strains from the Indian continent exist. This study comprises a comprehensive immunopathological characterization upon infection with two additional strains, the Ethiopian L. donovani L82 strain and the Nepalese L. donovani BPK282 strain in both Syrian hamsters and C57BL/6 mice. Parameters that include parasitaemia levels, weight loss, hepatosplenomegaly and alterations in cellular composition of the spleen and liver, showed that the L82 strain generated an overall more virulent infection compared to the BPK282 strain. Altogether, both L. donovani strains are suitable and interesting for subsequent in vivo investigation of visceral leishmaniasis in the Syrian hamster and the C57BL/6 mouse model.

Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure

“…Liver weights were also significantly elevated, whereas the absence of an increased spleen weight following CPA-treatment might be linked to suppression of lymphoproliferative responses. Given that almost no immunological work has been performed in the hamster model, to our knowledge this is the first report extracting immunological information on WBC composition of hamster blood by exploiting cross-reactivity of mouse monoclonal antibodies (Kauffmann et al, 2016).…”

“…After two cycles of lysis with erythrocyte lysis (EL) buffer (QIAamp RNA Blood Mini kit), white blood cells (WBCs) were suspended in RPMI-1640 without phenol-red, supplemented with 10% iFCS. After Fc-receptor blocking, the cell suspension was transferred into a flow cytometer tube, stained with the cell viability solution 7-AAD (BD Pharmingen™), fluorescein-labelled anti-CD4 (clone GK1.5) and phycoerythrin-labelled anti-MHC-II (clone 14-4-45) monoclonal mouse antibodies (mAbs) both showing cross-reactivity towards hamster antigens (eBioscience, Thermo Fisher Scientific) (Kauffmann et al, 2016). Hamsters were followed-up until 45 dpi after which parasite burdens in the main target organs (liver, spleen and bone marrow) were determined on Giemsa-stained tissue imprints.…”

Chemotherapy of leishmaniasis: present challenges

“…Within the parasite species chosen, we should also define which strain will be used, since even within the same species, virulence and behaviour can be variable, as well as response to treatment. Strains of L. donovani from India and Africa are good examples of this heterogeneity (Kauffmann et al 2016). It is important to keep in mind that Leishmania parasites kept under in vitro conditions can lose their virulence.…”