Multi-organ failure caused by the inflammatory
cytokine storm induced by severe
infection is the major cause of death for
sepsis. Sj-Cys is a
cysteine protease inhibitor secreted by Schistosoma japonicum with strong immunomodulatory functions on host immune system. Our previous studies have shown that treatment with Sj-Cys
recombinant protein (rSj-Cys) attenuated
inflammation caused by
sepsis. However, the immunological mechanism underlying the
immunomodulation of Sj-Cys for regulating inflammatory diseases is not yet known. In this study, we investigated the effect of Sj-Cys on the macrophage M2 polarization and subsequent
therapeutic effect on
sepsis. The rSj-Cys was expressed in yeast Pichia pastoris. Incubation of mouse bone marrow-derived macrophages (BMDMs) with yeast-expressed rSj-Cys significantly activated the polarization of macrophages to M2 subtype characterized by the expression of F4/80+ CD206+ with the elated secretion of
IL-10 and TGF-β. Adoptive transfer of rSj-Cys treated BMDMs to mice with
sepsis induced by cecal
ligation and
puncture (CLP) significantly improved their survival rates and the systemic clinical manifestations of
sepsis compared with mice receiving non-treated normal BMDMs. The
therapeutic effect of Sj-Cys-induced M2 macrophages on
sepsis was also reflected by the reduced pathological damages in organs of heart, lung, liver and kidney and reduced serological levels of tissue damage-related ALT, AST, BUN and Cr, associated with downregulated pro-inflammatory
cytokines (IFN-gamma and IL-6) and upregulated regulatory anti-inflammatory
cytokines (IL-10 and TGF-β). Our results demonstrated that Sj-Cys is a strong immunomodulatory
protein with anti-inflammatory features through activating M2 macrophage polarization. The findings of this study suggested that Sj-Cys itself or Sj-Cys-induced M2 macrophages could be used as therapeutic agents in the treatment of
sepsis or other inflammatory diseases.