Abstract
BackgroundSchistosome eggs are trapped in host liver and elicit severe hepatic granulomatous inflammation, which can lead to periportal fibrosis, portal hypertension, hemorrhage, or even death in the host. It was reported that the macrophage plays an important role in host immune responses to schistosome infection. Nitric oxide (NO) produced by classically activated macrophages (M1 macrophages) is cytotoxic to schistosomula and can prevent hepatic schistosomal fibrosis, while arginase-1 (Arg-1) expressed by alternatively activated macrophages (M2 macrophages) promotes hepatic schistosomal fibrosis. However, the dynamics of macrophage polarization, as well as the possible factors that regulate macrophage polarization, during schistosome infection remain unclear.MethodsWe first analyzed M1 and M2-phenotypic markers of peritoneal macrophages from mice infected with Schistosoma japonicum (S. japonicum) at indicated time points using flow cytometry (FCM) analysis and real-time PCR. Then we treated peritoneal macrophages from normal mice with schistosome worm antigen (SWA) or schistosome soluble egg antigen (SEA) and determined M1 and M2-phenotypic markers, in order to identify macrophage polarization in responding to schistosomal antigens.ResultsIn this study, we showed that macrophages were preferentially differentiated into the M1 subtype during the acute stage of S. japonicum infection. However, the level of M1 macrophages decreased and M2 macrophages significantly increased during the chronic stage of infection. Furthermore, we showed that SWA favors the generation of M1 macrophages, whereas SEA preferentially promotes M2-polarized phenotype.ConclusionThese findings not only reveal the parasite antigen-driven dynamic changes in macrophage polarization, but also suggest that manipulation of macrophage polarization may be of therapeutic benefit in controlling excessive hepatic granulomas and fibrosis in the host with schistosomiasis.
Highlights
Schistosome eggs are trapped in host liver and elicit severe hepatic granulomatous inflammation, which can lead to periportal fibrosis, portal hypertension, hemorrhage, or even death in the host
Similar results were obtained in mean fluorescence intensity (MFI) of CD16/32 and CD206 expression, which reflects the average level of CD16/32 and CD206 expressed on a single M1 or M2 macrophage cell, respectively (Figure 1A and 1C)
These results suggest that macrophages are typically skewed from the M1 phenotype at the acute stage of S. japonicum infection toward the M2 phenotype at the chronic stage
Summary
Schistosome eggs are trapped in host liver and elicit severe hepatic granulomatous inflammation, which can lead to periportal fibrosis, portal hypertension, hemorrhage, or even death in the host. Nitric oxide (NO) produced by classically activated macrophages (M1 macrophages) is cytotoxic to schistosomula and can prevent hepatic schistosomal fibrosis, while arginase-1 (Arg-1) expressed by alternatively activated macrophages (M2 macrophages) promotes hepatic schistosomal fibrosis. M1 macrophages that develop in response to pro-inflammatory stimuli such as LPS or IFN-γ are characterized by the expression of high levels of CD16/32, TNF-α, IL-12, inducible nitric oxide synthase (iNOS) and chemokines such as CXCL9, CXCL10 and CXCL11. M2 macrophages, can be induced by IL-4 or chitin, are characterized by their high expression of mannose receptor (Mrc encoding MR, known as CD206), arginase-1 (Arg-1), IL-10 and chemokines such as CCL2, CCL17 and CCL22 [11,12,13,14,15]
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