Possible Role for Toll-Like Receptors in Interaction of<i>Fasciola hepatica</i>Excretory/Secretory Products with Bovine Macrophages

Flynn, Robin J.; Mulcahy, Grace

doi:10.1128/iai.00732-07

Cited by 55 publications

(67 citation statements)

References 32 publications

(44 reference statements)

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“…Similarly, we have found that peritoneal cells from rats cultured in the presence of ESP or a purified protein-glutathione transferase, inhibit nitric oxide production induced by the TLR4 ligand, LPS [38]. Coincidently, other authors have shown that ESP from F. hepatica reduce the ability of bovine macrophages to produce nitric oxide (NO) or IFN-induced by LPS [39]. Also, the purified protein derivatives from Mycobacterium bovis (PPD-B), which are TLR 4 and 2 ligands, induce a rise in IL-10 production [39] (Fig.…”

Section: Helminth Infections: All Roads Lead To Alternatively Activatmentioning

confidence: 85%

New Insights into the Modulation of Immune Response by Fasciola hepatica Excretory-Secretory Products

Cervi¹,

Serradell²,

Guasconi³

et al. 2009

CIR

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Fasciola hepatica is a trematode that affects human and domestic ruminant health, causing significant economic losses in cattle estimated at US$2000 millon per year. Juvenile parasites migrating through the host tissues, as well as adults settle in the biliary ducts, are in contact with different cells from the immune system. Despite those interactions, the persistence of the parasite in the host for many years provides evidence of its ability to prevent or downmodulate the inflammatory response in the infection site. Different strategies have been developed by the parasite to prevent potential damage being induced by the immune response, thus allowing some parasites to reach the adult stage in a safe place such as the biliary ducts. In this review we discuss how excretory-secretory products (ESP) from F. hepatica can affect the functionality of pivotal immune cells, such as eosinophils and macrophages by inducing selective apoptosis pathways and alternative activation of macrophages. Furhermore, the modulatory effects of ESP on dendritic cell activation and lymphocyte proliferation is reviewed as a strategy to facilitate F. hepatica evasion of both innate and adaptive immunity.

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Section: Helminth Infections: All Roads Lead To Alternatively Activatmentioning

confidence: 85%

New Insights into the Modulation of Immune Response by Fasciola hepatica Excretory-Secretory Products

Cervi¹,

Serradell²,

Guasconi³

et al. 2009

CIR

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“…In contrast, macrophages activated by the interleukin-4 (IL-4)-dependent signal pathway are classified as alternatively activated macrophages (AAM) (14). The effects of F. hepatica tegumental antigen and excretory-secretory products on macrophages derived from mice, cattle, and ovines have been well documented (14,16,19,20,32,33). Moreover, recombinant versions of the parasite peroxiredoxin have been shown to induce the alternative activation of macrophages, as indicated by an in- A 492 nm a n t i -F h 1 5 a n t i -F h T g a n t i -E S P The ELISA plates were coated with 15 g/ml Fh12.…”

Section: Discussionmentioning

confidence: 99%

“…crease in arginase activity in murine (14,19) and ruminant (16,20) models. Recently, a homogenate of adult flukes has also been shown to induce arginase activity in bovine macrophages derived from nonvaccinated animals and cultured in vitro (34).…”

Section: Discussionmentioning

confidence: 99%

“…F. hepatica and other helminth-derived peptides have also shown to suppress the activation of macrophages by microbial stimuli and to alter the response of B cells to cytokine stimulation (17,18). Total ESPs and recombinant versions of thioredoxin peroxidase have been shown to induce the alternative activation of macrophages in murine (14,19) and ruminant (16,20) models of fascioliasis. The alternatively activated macrophages (AAM) are associated with the Th2-type immune responses that are typically induced by F. hepatica, as well as many other helminth parasites, and that are involved in controlling Th1-type immune responses (21).…”

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confidence: 99%

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

Figueroa-Santiago

Espino

2014

Infect Immun

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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).

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“…We stimulated BOMA monocytes/macrophages with Fh-ES what resulted in no TNF-α change, but LPS activated BOMA cells diminished release of TNF-α after Fh-ES stimulation. Flynn and Mulcahy (2008) proved that blood mononuclear cells stimulated with Fh-ES release IL-4 in a time related manner after infection. In the beginning of the infection no IL-4 was observed, the level of IL-4 reached its highest point in 2 nd or 6 th week and was decreasing until the 12 th week, when the infection became chronic.…”

Section: Discussionmentioning

confidence: 99%

Fasciola hepatica — the pilot study of in vitro assessing immune response against native and recombinant antigens of the fluke

Bąska

Zawistowska-Deniziak

Zdziarska

et al. 2013

Acta Parasitologica

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Fasciola hepatica is a liver fluke that infects 2.4 million of people and causes great economical loss in animal production. To date a 100% effective vaccine has not been developed and the disease is controlled by drug therapy. Great efforts are put into development of effective vaccine against parasite what is difficult since Fasciola spp. (like other helmints) during evolutionary process has developed sophisticated and efficient methods to evade immune response. During preliminary experiments it is convenient to use cell lines which are relatively cheap and allow for reproducible comparison of results between laboratories. We stimulated BOMA (bovine monocyte/macrophage cell line) and BOMAC (bovine macrophage cell line) with native or recombinant antigens of Fasciola hepatica and assessed IFN-γ, IL-4 and TNF-α level upon stimulation. We observed diminished secretion of proinflammatory TNF-α in LPS activated BOMA cells stimulated with Excretory/Secretory products of adult fluke (Fh-ES). We also observed greater changes in gene expression in LPS activated BOMA cells than in non activated BOMA cells upon stimulation using Fh-ES. The results show possibility of using cell lines for in vitro research of bovine immune response against liver fluke, although this model still requires validation and further characterization.

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Possible Role for Toll-Like Receptors in Interaction ofFasciola hepaticaExcretory/Secretory Products with Bovine Macrophages

Cited by 55 publications

References 32 publications

New Insights into the Modulation of Immune Response by Fasciola hepatica Excretory-Secretory Products

New Insights into the Modulation of Immune Response by Fasciola hepatica Excretory-Secretory Products

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

Fasciola hepatica — the pilot study of in vitro assessing immune response against native and recombinant antigens of the fluke

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