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THE PGE2/IL-10 AXIS DETERMINES SUSCEPTIBILITY OF B-1 CELL-DERIVED PHAGOCYTES (B-1CDP) TO LEISHMANIA MAJOR INFECTION
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Abstract
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 L. major required lipid bodies/PGE2 and IL-10 by
B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE2 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 L. 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 L. major infection, most likely via PGE2-driven production of IL-10.
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