Phagocytosis and activation of bone marrow‐derived macrophages by Plasmodium falciparum gametocytes

Abstract

Background 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. Similarly, activation of host macrophages by gametocytes has not yet been carefully addressed. Methods Phagocytosis 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. Results The 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. Conclusions These 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.

Basophil Depletion Alters Host Immunity, Intestinal Permeability, and Mammalian Host-to-Mosquito Transmission in Malaria

“…TNF-α and IFN-γ, for instance, have both previously been demonstrated to be involved with gametocyte killing in the mammalian host ( 68 , 69 ), with TNF-α being shown to impact transmission in rodent models ( 70 ). Macrophages in culture have been shown to phagocytose gametocytes and produce TNF-α, MIP-2, and NO in response to late-stage gametocytes, suggesting innate immune involvement in controlling sexual stage parasites ( 71 ). In our network analyses, plasma IL-17 and IL-10 in baso (−) mice at 3 d p.i.…”

Phagocytosis-associated genes in Acanthamoeba castellanii feeding on Escherichia coli

“…Several methods are frequently employed to detect phagosome, as well as phagolysosome formation. Giemsa staining has been traditionally used to observe such phenomena in numerous cell lines [ 18 ]. However, due to monochrome staining, accurately differentiating between amoebal mitochondria from E. coli was somewhat problematic.…”

Erythropoiesis and Malaria, a Multifaceted Interplay

“…Several studies reported the elevation of NO in blood upon Plasmodium infection in children with malarial anemia [ 144 , 145 ]. Interestingly, recent data show that P. falciparum gametocytes are phagocytosed by immortalised mouse BM-derived macrophages and late gametocytes initiate the production of NO, cytokines, and chemokines [ 146 ]. Although these data have to be confirmed in a more physiological human setting, they suggest that gametocytes may stimulate the secretion of erythropoiesis-inhibiting factors by macrophages constituting the erythroblastic islands, which are the specialised niches for erythropoiesis.…”