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

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.

In vivo and in vitro phagocytosis of Leishmania (Leishmania) amazonensis promastigotes by B‐1 cells

“…B‐1 cells‐derived phagocytes (B‐1 CDP) are capable of internalizing certain pathogens, including L. major . We evaluated whether this cell population was also permissive for infection with L. (L.) amazonensis promastigotes.…”

“…These cells had a significantly higher phagocytic index compared to peritoneal or medullar macrophages at 16 and 24 h. Few reports have described the phagocytosis of pathogens by B‐1 cells, so little knowledge is available concerning the functions and consequences of this process in immunity (especially in infectious diseases). B‐1 cells were able to differentiate into phagocytes that were highly susceptible to in vitro infection by Cryptococcus neoformans , Coxiella burnetii and L. major . However, the mechanisms used by these pathogens to enter B‐1 cells appeared to be different.…”

“…Although other cell types can also become infected with Leishmania species [i.e. neutrophils , fibroblasts and B‐1 cells ], the study of parasite infection in these latter cells has been neglected.…”

“…Recently, Arcanjo and collaborators demonstrated that B‐1 cells were able to phagocytose L. major promastigotes and that the process was dependent on IL‐10 production by these cells. Herein, we provide new information concerning the interactions between Leishmania promastigotes and B‐1 cells.…”

Dependency of B-1 Cells in the Maintenance of Splenic Interleukin-10 Producing Cells and Impairment of Macrophage Resistance in Visceral Leishmaniasis

“…It has been shown that IL-10-derived from B cells is capable to promote the development of suppressive responses associated with susceptibility to infection (Bankoti et al, 2012; Arcanjo et al, 2015). However, the identification of the B cell population involved in the susceptibility to VL is still vague and needs further studies.…”