B-1 cells modulate the murine macrophage response toLeishmania majorinfection

Abstract

AIMTo investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major (L. major) in vitro.METHODSPeritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE2) were determined using a PGE2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE2-neutralizing drugs inhibited PGE2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major.RESULTSWe report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major-infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE2 in supernatants of L. major-infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major-infected macrophages when the B-1 cells were isolated from IL-10 knockout mice.CONCLUSIONOur results show that elevated levels of PGE2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell cultures.

A Hard(y) Look at B-1 Cell Development and Function

“…A subset of body cavity B-1 cells appears to constitutively express IL-10, which may imbue them with regulatory functions (87). B-1 cell-derived IL-10 production has been associated with attenuated responses to infection with Leishmania (88, 89) and artherosclerosis (90), and it appears to enhance B-1 cell expansion via induction of proliferation (91). The term “innate response activator (IRA) B cell” was coined by Swirski and colleagues for B-1a cells from the body cavities that migrated in response to inflammatory cues and accumulated in the spleen and lung early in sepsis.…”

How to B(e)-1 Important Cell During Leishmania Infection

“…To further confirm this, B-1CDP from IL-10 −/− mice are significantly less susceptible to L. major than those from WT mice, with lower infection ratios and reduced parasite proliferation (Arcanjo et al, 2015). Macrophages derived from BALB/Xid mice appear to be less susceptible to L. major infection than those derived from WT BALB/c mice ( Figure 1C) (Arcanjo et al, 2017a). However, the presence of B-1 cells from WT BALB/c mice in the culture makes macrophages from both WT and BALB/Xid mice more susceptible to L. major infection in vitro and this phenomenon is not dependent on cell contact ( Figure 1C) (Arcanjo et al, 2017a).…”

“…Macrophages derived from BALB/Xid mice appear to be less susceptible to L. major infection than those derived from WT BALB/c mice ( Figure 1C) (Arcanjo et al, 2017a). However, the presence of B-1 cells from WT BALB/c mice in the culture makes macrophages from both WT and BALB/Xid mice more susceptible to L. major infection in vitro and this phenomenon is not dependent on cell contact ( Figure 1C) (Arcanjo et al, 2017a). Through the use of anti-IL-10 and nonsteriodal anti-inflammatory drugs, it was again confirmed that this effect on macrophage susceptibility was due to IL-10 and PGE 2 (Arcanjo et al, 2017a).…”

“…Several studies have suggested a role of B cells in promoting infection with Leishmania spp. either directly or indirectly via production of antibody, IL-10 or PGE 2 (Hoerauf et al, 1994(Hoerauf et al, , 1995Palanivel et al, 1996;Smelt et al, 2000;Colmenares et al, 2002;Buxbaum and Scott, 2005;Wanasen et al, 2008;Chu et al, 2010;Deak et al, 2010;Arcanjo et al, 2015Arcanjo et al, , 2017aGonzaga et al, 2015Gonzaga et al, , 2017Geraldo et al, 2016). Taking CL as example, B cells are thought to be harmful to the host response.…”

“…Furthermore, in VL caused by L. donovani it is known that: mice which lack B cells are more resistant to infection (Smelt et al, 2000); marginal zone B cells impairs T cell responses (Bankoti et al, 2012); and the antibody production (Srinontong et al, 2018) as well as the presence of B cells (Silva-Barrios et al, 2016) are linked to pathogenesis. Besides conventional B-2 cells, B-1 cells also seem to be very important in this context (Hoerauf et al, 1994;Arcanjo et al, 2015Arcanjo et al, , 2017aGonzaga et al, 2015Gonzaga et al, , 2017Geraldo et al, 2016) and here we visit several works trying to summarize the main findings in the field.…”