The PGE(2)/IL-10 Axis Determines Susceptibility of B-1 Cell-Derived Phagocytes (B-1CDP) to Leishmania major Infection

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2015-05-01
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Arcanjo, Angelica F.
LaRocque-de-Freitas, Isabel F.
Rocha, Juliana Dutra B.
Zamith, Daniel
Costa-da-Silva, Ana Caroline
Nunes, Marise Pinheiro
Mesquita-Santos, Fabio P.
Morrot, Alexandre
Filardy, Alessandra A.
Mariano, Mario [UNIFESP]
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B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP) has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro. the data obtained in this study demonstrate that B-1CDP cells are more susceptible to infection than peritoneal macrophages, since B-1CDP cells have a higher number of intracellular amastigotes forms and consequently release a larger number of promastigotes. Exacerbated infection by Leishmania major required lipid bodies/PGE(2) and IL-10 by B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE(2) production was blocked by NSAIDs. the involvement of IL-10 in this mechanism was confirmed, since B-1CDP cells from IL-10 KO mice are more competent to control Leishmania major infection than cells from wild type mice. These findings further characterize the B-1CDP cells as an important mononuclear phagocyte that plays a previously unrecognized role in host responses to Leishmania major infection, most likely via PGE(2)-driven production of IL-10.
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Plos One. San Francisco: Public Library Science, v. 10, n. 5, 18 p., 2015.