Purification of Native Fasciola hepatica Fatty Acid-Binding Protein and Induction of Alternative Activation of Human Macrophages

2020 ◽  
pp. 149-169
Author(s):  
Olgary Figueroa-Santiago
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Alternative Activation ◽  
Fatty Acid Binding ◽  
Human Macrophages ◽  
Acid Binding Protein

scholarly journals Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

2014 ◽  
Vol 82 (12) ◽  
pp. 5005-5012 ◽  
Author(s):  
Olgary Figueroa-Santiago ◽  
Ana M. Espino
Keyword(s):  
Nitric Oxide ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Alternative Activation ◽  
Interleukin 12 ◽  
Fatty Acid Binding ◽  
Content Type ◽  
Acid Binding Protein

ABSTRACTThe liver flukeFasciola hepaticais a highly evolved parasite that uses sophisticated mechanisms to evade the host immune response. The immunosuppressive capabilities of the parasite have been associated with antigens secreted through the parasite's tegument, called excretory-secretory products (ESPs). Proteomic studies have identified the fatty acid binding protein (FABP) as one of molecules present in the parasite ESPs. Although FABP has been investigated for potential use in the development of vaccines against fascioliasis, its direct interaction with cells of immune system has not been studied. In this study, FABP was purified in native form from soluble extracts ofF. hepaticaadult flukes using a combination of molecular sieving chromatography and preparative isoelectric focusing. The immunological effect of the purified protein, termed Fh12, was assayedin vitrousing monocyte-derived macrophages (MDM) obtained from healthy human donors. Results from the assay indicate that Fh12 produced a significantly increased arginase expression and activity and induced the expression of chitinase-3-like protein (CHI3L1). The assay also showed that Fh12 downregulated the production of nitric oxide (NO) and the expression of nitric oxide synthase (NOS2). This indicates that Fh12 induced the production of alternatively activated macrophages (AAMϕ). The results also demonstrated the ability of Fh12 to downregulate the secretion of the proinflammatory and inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1βB, even after stimulation with lipopolysaccharide (LPS), as well as its ability to stimulate the overexpression of IL-10. These results suggest a potent anti-inflammatory role for Fh12, which could occur via targeting of Toll-like receptor 4 (TLR4).

A Fasciola hepatica-derived fatty acid binding protein induces protection against schistosomiasis caused by Schistosoma bovis using the adjuvant adaptation (ADAD) vaccination system

2014 ◽  
Vol 145 ◽  
pp. 145-151 ◽  
Author(s):  
Belén Vicente ◽  
Julio López-Abán ◽  
José Rojas-Caraballo ◽  
Luis Pérez del Villar ◽  
George V. Hillyer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Schistosoma Bovis

scholarly journals Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Belén Vicente ◽  
Julio López-Abán ◽  
Jose Rojas-Caraballo ◽  
Esther del Olmo ◽  
Pedro Fernández-Soto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Schistosoma Mansoni ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Delivery Systems ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Adaptive Immune Stimulation Is Required To Obtain High Protection with Fatty Acid Binding Protein Vaccine Candidate Against Fasciola hepatica In Balb/C Mice

2012 ◽  
Vol 98 (3) ◽  
pp. 527-535 ◽  
Author(s):  
Julio López-Abán ◽  
Ana Esteban ◽  
Belén Vicente ◽  
José Rojas-Caraballo ◽  
Esther del Olmo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Vaccine Candidate ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Immune Stimulation ◽  
Protein Vaccine ◽  
Fatty Acid Binding ◽  
Adaptive Immune ◽  
Acid Binding Protein

Immunoprophylaxis against Fasciola hepatica in Rabbits Using a Recombinant Fh15 Fatty Acid-Binding Protein

2001 ◽  
Vol 87 (3) ◽  
pp. 697 ◽  
Author(s):  
P. Casanueva ◽  
G. V. Hillyer ◽  
V. Ramajo ◽  
A. Oleaga ◽  
E. Y. Espinoza ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

scholarly journals Recombinant Fasciola hepatica fatty acid binding protein (Fh15) as a novel anti-inflammatory biotherapeutic in an acute gram-negative non-human primate sepsis model

2021 ◽  
Author(s):  
Jose J. Rosado-Franco ◽  
Albersy Armina-Rodriguez ◽  
Nicole Marzan-Rivera ◽  
Armando Burgos ◽  
Natalie Spiliopoulos ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Immune Cell ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Rhesus Macaques ◽  
Fatty Acid Binding ◽  
Gram Negative ◽  
Acid Binding Protein ◽  
Anti Inflammatory

Due to their phylogenetic proximity to human, non-human primates (NHP) are considered and adequate choice for basic and pre-clinical model of sepsis. Gram-negative bacteria are the primary causative of sepsis. During infection bacteria continuously release the potent toxin lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to death. Our previous research has demonstrated in vitro and in vivo using a mouse model of septic shock that Fh15, a recombinant variant of Fasciola hepatica fatty acid binding protein, acts as an antagonist of TLR4 suppressing the LPS-induced pro-inflammatory storm. The present study aimed to demonstrate that Fh15 suppress the cytokine storm and other inflammatory markers during the early phase of endotoxemia induced in rhesus macaques by i.v. infusion with lethal doses of live E. coli. Fh15 was administered as isotonic infusion 30 min prior to the bacterial infusion. Among the novel findings reported in this communication, I) Fh15 significantly prevents bacteremia, suppressed LPS levels in plasma and the production of C-reactive protein and procalcitonin, which are key signature of inflammation and bacterial infection, respectively, II) notably reduced the production of pro-inflammatory cytokines, and III) increased innate immune cell populations in blood, which suggest a role in promoting a prolonged steady state in rhesus macaques even in the presence of inflammatory stimuli. THis is the first report demonstrating that a F. hepatica-derived molecule possesses potential as anti-inflammatory drug against endotoxemia in an NHP model.

Sign in / Sign up

Export Citation Format

Share Document