Fasciola hepatica Fatty Acid Binding Protein 1 Modulates T cell Polarization by Promoting Dendritic Cell Thrombospondin-1 Secretion Without Affecting Metabolic Homeostasis in Obese Mice.

Autor:	Zawistowska-Deniziak A; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Lambooij JM; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Kalinowska A; Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland., Patente TA; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Łapiński M; International Institute of Molecular and Cell Biology, Warsaw, Poland., van der Zande HJP; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Basałaj K; Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland., de Korne CM; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands.; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands., Chayé MAM; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Gasan TA; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Norbury LJ; Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland.; School of Science, STEM College, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, VIC, Australia., Giera M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Zaldumbide A; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., Smits HH; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands., Guigas B; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Leiden University Center for Infectious Diseases (LU-CID), Leiden, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 26; Vol. 13, pp. 884663. Date of Electronic Publication: 2022 May 26 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.884663
Abstrakt:	Background: The parasitic trematode Fasciola hepatica evades host immune defenses through secretion of various immunomodulatory molecules. Fatty Acid Binding Proteins ( fh FABPs) are among the main excreted/secreted proteins and have been shown to display anti-inflammatory properties. However, little is currently known regarding their impact on dendritic cells (DCs) and their subsequent capacity to prime specific CD4 + T cell subsets. Methodology/principal Findings: The immunomodulatory effects of both native F. hepatica extracts and recombinant fh FABPs were assessed on monocyte-derived human DCs (moDCs) and the underlying mechanism was next investigated using various approaches, including DC-allogenic T cell co-culture and DC phenotyping through transcriptomic, proteomic and FACS analyses. We mainly showed that fh FABP1 induced a tolerogenic-like phenotype in LPS-stimulated moDCs characterized by a dose-dependent increase in the cell-surface tolerogenic marker CD103 and IL-10 secretion, while DC co-stimulatory markers were not affected. A significant decrease in secretion of the pro-inflammatory cytokines IL-12p70 and IL-6 was also observed. In addition, these effects were associated with an increase in both Th2-on-Th1 ratio and IL-10 secretion by CD4 + T cells following DC-T cell co-culture. RNA sequencing and targeted proteomic analyses identified thrombospondin-1 (TSP-1) as a non-canonical factor highly expressed and secreted by fh FABP1-primed moDCs. The effect of fh FABP1 on T cell skewing was abolished when using a TSP-1 blocking antibody during DC-T cell co-culture. Immunomodulation by helminth molecules has been linked to improved metabolic homeostasis during obesity. Although fh FABP1 injection in high-fat diet-fed obese mice induced a potent Th2 immune response in adipose tissue, it did not improved insulin sensitivity or glucose homeostasis. Conclusions/significance: We show that fh FABP1 modulates T cell polarization, notably by promoting DC TSP-1 secretion in vitro , without affecting metabolic homeostasis in a mouse model of type 2 diabetes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zawistowska-Deniziak, Lambooij, Kalinowska, Patente, Łapiński, van der Zande, Basałaj, de Korne, Chayé, Gasan, Norbury, Giera, Zaldumbide, Smits and Guigas.)
Databáze:	MEDLINE
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