Broad Antagonistic Activity of a Fatty Acid Binding Protein of Fasciola hepatica (Fh12) in the Presence of Whole Bacteria Extract Prelude a Broad Spectrum of Action
Authors: Ruiz‐Jiménez Caleb , Aguayo Vasti , Valdés Bianca , Espino Ana M. 
Published: June 2021

Inflammation process could be initiated by activation of single or multiple toll‐like receptors on antigen presenting cells via molecular pattern recognition of molecules of foreign pathogens like Gram positive and negative bacteria. The exacerbated immune response to these molecules can lead to septic shock syndrome that could be fatal. The identification of TLR‐antagonists that could block or diminish the activation of these receptors and suppress the inflammatory mediators has become in an excellent therapeutic alternative against sepsis. In the last decade, scientists have shown interest in the strong anti‐inflammatory role that some helminth parasites exhibit. Helminths use several immunomodulatory strategies to modify immune responses in order to survive into the mammalian host. Fasciola hepatica is able to induce long‐lasting disease in the host associated to Th2 responses, which is linked to an anti‐inflammatory phenotype of immune responses. This parasite secretes and expresses proteins on their surfaces that are essential either, its metabolism or immunomodulating the host's immune response. One of these proteins is a 12kDa fatty acid binding protein (Fh12). We had previously demonstrated that Fh12 could suppress the TLR4 activation. The current study aimed to ascertain whether Fh12 could also suppress other TLRs. THP1‐Blue CD14 cells is a cell line of human monocytes that express NF‐κB/AP‐1 inducible secreted embryonic alkaline phosphatase (SEAP) reporter gene. Cells were cultured for 18h, 37°C, 5% CO2 with 10μg Fh12 in the presence or absence of specific ligands for each TLR as well as with or without heat attenuated whole extracts of (1 × 108 cells) Escherichia coli, Klebsiella pneumonia or Enterococcus faecalis. Cells cultured only with RPMI‐medium, TLR‐ligands, Fh12 or whole bacteria extracts alone served as controls. Results demonstrated that Fh12 was capable to significantly suppress the activation of NF‐κB to Gram negative and Gram‐positive bacteria by 65% and 90%, respectively. In consistency with this finding Fh12 also suppressed the NF‐κB activation induced by specific ligands for TLR2, TLR4, TLR5, TLR6 and TLR8 by 80% to 89% respectively. FACS analysis also revealed that Fh12 also induced significant reduction in the expression of co‐stimulatory molecules like CD40, CD80 and CD86, which play crucial role in the initiation and maintenance of inflammatory immune response. Our results suggest that Fh12 not only impacts TLR4, but also could impact multiple TLRs and which prelude a broader anti‐inflammatory effect for Fh12. Further studies directed to explore the potential of Fh12 as a new class of drug against septic shock caused by bacteria and also others inflammatory diseases are under study.

Support or Funding Information

This study was supported by MBRS‐RISE R25GM061838‐13, and NIH grants G12MD007600 and 2P40OD012217.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.