The PGE2/IL-10 Axis Determines Susceptibility of B-1 Cell-Derived Phagocytes (B-1CDP) to Leishmania major Infection

PLoS One. 2015 May 1;10(5):e0124888. doi: 10.1371/journal.pone.0124888. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / parasitology*
  • Dinoprostone / metabolism*
  • Disease Susceptibility
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / metabolism*
  • Leishmania major / drug effects
  • Leishmania major / growth & development
  • Leishmania major / immunology
  • Leishmania major / physiology*
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / parasitology*
  • Lipid Droplets / metabolism
  • Macrophages, Peritoneal / parasitology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parasitemia / immunology
  • Parasitemia / parasitology
  • Phagocytes / drug effects
  • Phagocytes / parasitology*
  • Phenotype
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Interleukin-10
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Aspirin

Grants and funding

This work was supported by Brazilian National Research Council (CNPq) and Rio de Janeiro State Science Foundation (FAPERJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.