Abstract
BackgroundThe innate immune response against various life cycle stages of the malaria parasite plays an important role in protection against the disease and regulation of its severity. Phagocytosis of asexual erythrocytic stages is well documented, but little and contrasting results are available about phagocytic clearance of sexual stages, the gametocytes, which are responsible for the transmission of the parasites from humans to mosquitoes. Similarly, activation of host macrophages by gametocytes has not yet been carefully addressed.MethodsPhagocytosis of early or late Plasmodium falciparum gametocytes was evaluated through methanol fixed cytospin preparations of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated for 2 h with P. falciparum and stained with Giemsa, and it was confirmed through a standardized bioluminescent method using the transgenic P. falciparum 3D7elo1-pfs16-CBG99 strain. Activation was evaluated by measuring nitric oxide or cytokine levels in the supernatants of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated with early or late gametocytes.ResultsThe results showed that murine bone marrow-derived macrophages can phagocytose both early and late gametocytes, but only the latter were able to induce the production of inflammatory mediators, specifically nitric oxide and the cytokines tumour necrosis factor and macrophage inflammatory protein 2.ConclusionsThese results support the hypothesis that developing gametocytes interact in different ways with innate immune cells of the host. Moreover, the present study proposes that early and late gametocytes act differently as targets for innate immune responses.
Highlights
The innate immune response against various life cycle stages of the malaria parasite plays an important role in protection against the disease and regulation of its severity
Evaluation of GCT phagocytosis using a luminescent‐based bioassay The bioassay to quantify GCT phagocytosis by bone marrow (BM)-derived macrophages (BMDM) was set up using luminescent late GCT (> 95 % stage V) from the transgenic P. falciparum 3D7elo1-pfs16-CBG99 strain cultured with BMDM in shaking conditions
The phagocytic activity of BMDM was confirmed by using latex beads
Summary
The innate immune response against various life cycle stages of the malaria parasite plays an important role in protection against the disease and regulation of its severity. Phagocytosis of asexual erythrocytic stages is well documented, but little and contrasting results are available about phagocytic clearance of sexual stages, the gametocytes, which are responsible for the transmission of the parasites from humans to mosquitoes. The life cycle of Plasmodium involves two hosts, the mosquito vector and a vertebrate. After rounds of asexual intraerythrocytic replication, a small proportion of Corbett et al Malar J (2021) 20:81 parasites develop into sexual forms called gametocytes (GCT). Stage V GCT circulate for several days until they are taken up by the vector, where the sporogonic sexual cycle occurs leading to the production of sporozoites, which can be injected into a new host. GCT are present in the BM of malaria patients [5, 6], including anaemic children [7]
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