Deletion of fibrinogen-like protein 2, a novel CD4+ CD25+ Treg effector molecule, leads to improved control of Echinococcus mutilocularis infection (MPF7P.718)

Abstract

Abstract The proliferation of Echinococcus multilocularis (E. multilocularis) metacestode is dependent on the nature/function of the periparasitic immune-mediated processes. Fibrinogen-like protein 2 (FGL2) was found to be up-regulated after E. multilocularis infection, however little is known about the contribution of this novel CD4+CD25+ Treg effector molecule to the control of a helminth infection. We showed that, as compared to AE-WT mice, AE-fgl2-deficient mice exhibited a significantly decreased parasite load and proliferation activity, associated with increased T cell proliferation in response to ConA, reduced Treg numbers and function, relative Th1 polarization, and increased B cell number and DC maturation. We showed for the first time that FGL2 is involved in negative immune regulation towards a helminth parasite and that IL-17A contributes to FGL2 regulation. By promoting Treg cell activity, FGL2 appears as a key-player in the immune orchestration of the outcome of E. multilocularis infection and measurement of plasma FGL2 levels might be useful to assess disease progression. Furthermore, targeting FGL2 could also be used for the development of novel treatment approaches in alveolar echinococcosis and other diseases caused by parasite pathogens.