Abstract
The increasing use of immunosuppressants in areas where visceral leishmaniasis (VL) is endemic has increased the number of people susceptible to developing more severe forms of the disease. Few studies have examined the quality of the immune response in immunosuppressed patients or experimental animals with VL. The present work characterises the parasite load developed in, and immune response to, Leishmania infantum-induced VL in C57BL/6 mice that, prior to and during infection, received immunosuppressant treatment with methylprednisolone (MPDN), anti-tumour necrosis factor (anti-TNF) antibodies, or methotrexate (MTX). The latter two treatments induced a significant reduction in the number of CD4+ T lymphocytes over the infection period. The anti-TNF treatment was also associated with a higher parasite load in the liver and a lower parasite load in the spleen. This, plus a possibly treatment-induced reduction in the number of cytokine-producing Th1 cells in the spleen, indicates the development of more severe VL. Interestingly, the MPDN and (especially) MTX treatments provoked a greater presence of soluble Leishmania antigen-specific multi-cytokine-producing T cells in the spleen and a lower liver parasite load than in control animals. These results highlight the need to better understand how immunosuppressant treatments might influence the severity of VL in human patients.
Highlights
Leishmaniasis is a neglected—though widely distributed—tropical disease caused by protozoan parasites of the genus Leishmania [1]
Patients who are immunosuppressed are at greater risk of developing visceral leishmaniasis (VL) when infected with Leishmania
Prior infection with HIV has been traditionally associated with an increased risk of developing VL, but the use of immunosuppressants in the treatment of autoimmune disease has been linked to a higher incidence of VL in Leishmania-endemic areas
Summary
Leishmaniasis is a neglected—though widely distributed—tropical disease caused by protozoan parasites of the genus Leishmania [1]. Co-infection with HIV increases by some 100–2320 fold the chances of developing active VL [5,6]. An increase in cases of VL has been detected among recipients of solid organ transplants [7,8] and patients receiving immunosuppressants to treat autoimmune diseases such as rheumatoid arthritis, lupus erythematous and inflammatory bowel disease [9,10]. Ever more frequently used in these contexts, these drugs may increase the number of people susceptible to Leishmania infection as well as condition the severity of disease. VL caused by both L. infantum and L. donovani has been reported in patients treated with methylprednisolone (MPDN) for rheumatoid arthritis, along with reactivated disease, likely due to the immunosuppression induced [11,12]
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