4.4 Article

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

Journal

MALARIA JOURNAL
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12936-021-03589-2

Keywords

Malaria; Plasmodium falciparum gametocytes; Immortalized mouse C57Bl; 6 bone marrow-derived macrophages; Phagocytosis; Nitric oxide; Tumour necrosis factor-alpha; Macrophage inflammatory protein 2

Funding

  1. Fondazione Cariplo [2017 -0846]
  2. Ministero dell'Istruzione, dell'Universita e della Ricerca [PRIN 2015.4JRJPP_004]
  3. Ministero degli Affari Esteri e della Cooperazione Internazionale [00949-2018]

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The study suggests that developing gametocytes interact differently with host innate immune cells and early and late gametocytes act differently as targets for innate immune responses.
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.

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