Schistosomes control inflammation in their hosts highly effective mechanisms such as induction of Tregs, Bregs, and alternatively activated macrophages (AAMs). Notably, IPSE/alpha-1, the major secretory product from eggs, triggers basophils to release interleukin (IL)-4 and IL-13. Both cytokines are essential for AAM induction, suggesting an important role for IPSE/alpha-1 in inflammation control. Here, we show by co-culture experiments that IPSE/alpha-1-induced basophil IL-4/IL-13 inhibited pro-inflammatory cytokine release from human LPS-activated monocytes. This effect was cell/cell contact-independent but dependent on IL-4, since it was abrogated in the presence of anti-IL-4 antibodies. Importantly, the IPSE/alpha-1-induced IL-4/IL-13 release from basophils was amplified in the presence of LPS. Moreover, monocytes co-cultured in the presence of LPS with IPSE/alpha-1-stimulated basophils adopted an AAM-like phenotype as assessed by elevated expression of CD206 and CD209. The putative relevance of these findings was supported by immunohistological staining of -infected murine tissue revealing close physical contact between IPSE/alpha-1 and basophils in schistosome egg granulomas. Taken together, we found that IPSE/alpha-1 dampens inflammatory cytokine responses by triggering basophil IL-4/IL-13, in particular in the context of TLR activation, thereby turning inflammatory monocytes into anti-inflammatory AAMs. This might represent a mechanism used by schistosomes to control inflammation in the host.
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http://dx.doi.org/10.3389/fimmu.2018.02293 | DOI Listing |
Front Immunol
October 2019
Experimental Pneumology, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany.
Schistosomes control inflammation in their hosts highly effective mechanisms such as induction of Tregs, Bregs, and alternatively activated macrophages (AAMs). Notably, IPSE/alpha-1, the major secretory product from eggs, triggers basophils to release interleukin (IL)-4 and IL-13. Both cytokines are essential for AAM induction, suggesting an important role for IPSE/alpha-1 in inflammation control.
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