Abstract
Visceral leishmaniasis (VL) is caused by parasitic protozoa of the genus Leishmania and is characterized by clinical manifestations such as fever, hepatosplenomegaly and anemia. Hemophagocytosis, the phenomenon of phagocytosis of blood cells by macrophages, is found in VL patients. In a previous study we established an experimental model of VL, reproducing anemia in mice for the first time, and identified hemophagocytosis by heavily infected macrophages in the spleen as a possible cause of anemia. However, the mechanism for parasite-induced hemophagocytosis or its role in parasite survival remained unclear. Here, we established an in vitro model of Leishmania-induced hemophagocytosis to explore the molecules involved in this process. In contrast to naïve RAW264.7 cells (mouse macrophage cell line) which did not uptake freshly isolated erythrocytes, RAW264.7 cells infected with L. donovani showed enhanced phagocytosis of erythrocytes. Additionally, for hemophagocytes found both in vitro and in vivo, the expression of signal regulatory protein α (SIRPα), one of the receptors responsible for the ‘don’t-eat-me’ signal was suppressed by post-transcriptional control. Furthermore, the overlapped phagocytosis of erythrocytes and Leishmania parasites within a given macrophage appeared to be beneficial to the parasites; the in vitro experiments showed a higher number of parasites within macrophages that had been induced to engulf erythrocytes. Together, these results suggest that Leishmania parasites may actively induce hemophagocytosis by manipulating the expression of SIRPα in macrophages/hemophagocytes, in order to secure their parasitism.
Highlights
Visceral leishmaniasis (VL), known as kala-azar, is caused by parasitic protozoa of the genus Leishmania
The hemophagocytic activity of RAW264.7 cells was tested to determine whether L. donovani infection induces hemophagocytosis by macrophages in vitro
When RAW264.7 cells were cultured with L. donovani expressing EGFP (Ld/egfp) and IFN-γ, it was observed that more cells had phagocytosed erythrocytes (Fig 1, lower panels)
Summary
Visceral leishmaniasis (VL), known as kala-azar, is caused by parasitic protozoa of the genus Leishmania. Endemic countries of VL include India, Bangladesh, Nepal, Brazil, Ethiopia and Sudan. It is estimated that there are 50,000 to 90,000 new cases of VL and 26,000 to 65,000 deaths annually [1]. The parasites develop as promastigotes in the midgut of sand flies, the insect vector for Leishmania. Following a blood meal by sand flies, the parasites causing VL are transmitted to the mammalian host where they proliferate as amastigotes within macrophages in the spleen, liver and bone marrow. VL is characterized by clinical manifestations such as fever, weight loss, hepatosplenomegaly and anemia
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