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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Infect+Immun
2014 ; 82
(12
): 5005-12
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Fasciola hepatica fatty acid binding protein induces the alternative activation
of human macrophages
#MMPMID25225247
Figueroa-Santiago O
; Espino AM
Infect Immun
2014[Dec]; 82
(12
): 5005-12
PMID25225247
show ga
The liver fluke Fasciola hepatica is 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 of F. hepatica adult flukes using a
combination of molecular sieving chromatography and preparative isoelectric
focusing. The immunological effect of the purified protein, termed Fh12, was
assayed in vitro using 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 (AAM?). The results also demonstrated the ability of Fh12
to downregulate the secretion of the proinflammatory and inflammatory cytokines
tumor necrosis factor alpha (TNF-?), interleukin-12 (IL-12), and IL-1?B, 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).