

@article {2941,
	title = {Deletion of {Fibrinogen}-like {Protein} 2 ({FGL}-2), a {Novel} {CD}4+ {CD}25+ {Treg} {Effector} {Molecule}, {Leads} to {Improved} {Control} of {Echinococcus} multilocularis {Infection} in {Mice}},
	journal = {PLoS neglected tropical diseases},
	volume = {9},
	number = {5},
	year = {2015},
	month = {may},
	pages = {e0003755},
	abstract = {BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/FINDINGS: Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS: FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.},
	keywords = {Animals, Antigens, CD4, Concanavalin A, Dendritic Cells, Echinococcosis, Echinococcus multilocularis, Fibrinogen, Flow Cytometry, Hepatic, Interleukin-17, Mice, Regulatory, T-Lymphocytes, Th1 Cells, Th17 Cells, Th2 Cells},
	issn = {1935-2735},
	doi = {10.1371/journal.pntd.0003755},
	author = {Wang, Junhua and Vuitton, Dominique A. and M{\"u}ller, Norbert and Hemphill, Andrew and Spiliotis, Markus and Blagosklonov, Oleg and Grandgirard, Denis and Leib, Stephen L. and Shalev, Itay and Levy, Gary and Lu, Xiaomei and Lin, Renyong and Wen, Hao and Gottstein, Bruno}
}
