Fasciola hepaticaGST mu-class suppresses the cytokine storm induced byE. coli-lipopolysaccharide whereas modulates the dynamic of peritoneal macrophages in a mouse model and suppresses the classical activation of macrophages

Abstract

Fasciola hepaticais known to suppresses antigen specific Th1 responses in concurrent bacterial infections while promoting the Th2/Treg regulatory responses. We have recently demonstrated that a single intraperitoneal injection with native F. hepatica glutathione S-transferase (nFhGST) mu-class, can suppresses the cytokine storm and increasing the survival rate in a mouse model of septic shock. Knowing that the peritoneal macrophages play essential roles in the defense against microbial agents, the present study aimed to determine whether nFhGST could modulate the dynamic of these cells. The remarkable findings in this article are, (i) nFhGST suppresses serum IL-12, TNFa, and IFN-g in BALB/c septic mice, whereas concurrently prevent the disappearance of large peritoneal macrophages and significantly increasing this population in the peritoneal cavity of LPS-treated animals, (ii) nFhGST was able to significantly suppresses the high levels of LPS-induced IL-10, which is considered a key cytokine in the pathophysiology of sepsis. (iii) nFhGST suppresses the classical activation of macrophagesin vitroby expressing high levels ofYm-1, a typical M2-type marker, secreting the production of IL-37, and preventing the production of TNFa, iNOS2 and nitric oxide, which are typical markers of M1-type macrophages, (iv) nFhGST suppresses the bacterial phagocytosis of macrophages, thus partially affecting the capacity of macrophages in destroying microbial pathogens. These findings demonstrate that nFhGST that nFhGST is an excellent modulator of the peritoneal macrophages contentin vivo, reinforcing the capacity of nFhGST as an anti-inflammatory drug against sepsis in animal models.