The<i>Fasciola hepatica</i>Tegumental Antigen Suppresses Dendritic Cell Maturation and Function

Hamilton, C. M.; Dowling, David J.; Loscher, Christine E.; Morphew, Russell M.; Brophy, Peter M.; O’Neill, Sandra M.

doi:10.1128/iai.00919-08

Cited by 106 publications

(143 citation statements)

References 51 publications

(63 reference statements)

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“…Our results suggest that in T cell-mast cell communication both the mast cell-derived cytokines and cell-tocell contact are crucial to induce sufficient immune responses, as we showed that the inhibition of cytokine secretion and cell surface molecule upregulation by FhTeg both impaired the mast cells' ability to prime T cells. Our study supports previous findings demonstrating that FhTeg can suppress Th1 immunity in vivo by directly rendering innate immune cells, such as dendritic cells, hyporesponsive to TLR activation (25), a characteristic of helminth-activated dendritic cells (37).…”

Section: Discussionsupporting

confidence: 80%

“…Currently, the focus is on elucidating FhTeg's function and role in immunomodulation. We have demonstrated the Th1-suppressive effect of FhTeg in vivo by inhibiting the release of proinflammatory cytokines in the mouse model of septic shock (25). We also demonstrated that FhTeg alters the ability of dendritic cells to prime Th1 immune responses by rendering them hyporesponsive to TLR activation, suppressing the production of a select panel of inflammatory cytokines and costimulatory molecules.…”

Section: Ast Cells Are Associated With Helminth Infection Butmentioning

confidence: 89%

“…The sup-pressive effect is not mediated through the common MAPKs found in the TLR pathway and is independent of MyD88 and TLR4. We have shown that FhTeg suppresses the transcription factor NF-kB p65, which is involved in the transcription of many Th1-promoting factors (25). This study examines FhTeg's interaction with mast cells to determine if its modulatory effect can impair mast cells' ability to promote Th1 immunity, and the possible mechanism involved in this process will be discussed.…”

Section: Ast Cells Are Associated With Helminth Infection Butmentioning

confidence: 99%

“…We previously showed that FhTeg suppresses the activation of NF-kB in LPS-stimulated dendritic cells (25), and this was examined in mast cells. It was first confirmed that BP can induce NF-kB p65 (at 15 and 30 min) expression in BMMCs (Fig.…”

Section: The Fhteg Suppressive Effect Is Not Specific To Nf-kb P65 Exmentioning

confidence: 99%

“…FhTeg was prepared as previously published (25). Endotoxin levels were determined using the PyroGene Endotoxin Detection System (Cambrex/ Lonza, Walkersville, MD).…”

Section: Animals and Agsmentioning

confidence: 99%

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Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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The parasitic worm Fasciola hepatica induces strong Th2 and T-regulatory immune responses while simultaneously suppressing Th1-driven immune responses to bystander microbial infections. It also prevents the initiation of Th1-mediated autoimmune disorders in mice through the suppression of Th17 and Th1 immune responses, and this can be mimicked by parasite-derived molecules. We have isolated F. hepatica tegumental coat Ag (FhTeg) and demonstrated its suppressive effect in vivo by directly targeting dendritic cells, impairing their ability to drive Th1 responses. Mast cells are critical in promoting Th1 protective immunity during bacterial infection and in driving Th1-mediated pathological conditions in autoimmune diseases. In this article, we show that FhTeg inhibits the ability of mast cells to drive the Th1 immune response by suppressing cytokine secretion (TNF-α, IL-6, IFN-γ, and IL-10) and ICAM1 expression in mast cells stimulated with LPS or heat-inactivated Bordetella pertussis Ag. These heat-inactivated B. pertussis Ag/LPS–stimulated mast cells fail to promote Th1 immune responses in CD4+ T cells when pretreated with FhTeg, and a role for ICAM1 in this process was demonstrated. FhTeg suppresses the activation of transcription factors in the TLR signaling pathway, which explains the decrease in cytokine production and cell surface marker expression. We demonstrated that FhTeg suppresses MAPK and NF-κB activation and enhances SOCS3 expression, which could explain its negative effect on the TLR pathways. We conclude that FhTeg targets innate immune cells, inhibiting their ability to drive Th1 immune responses.

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Section: Discussionsupporting

confidence: 80%

Section: Ast Cells Are Associated With Helminth Infection Butmentioning

confidence: 89%

Section: Ast Cells Are Associated With Helminth Infection Butmentioning

confidence: 99%

Section: The Fhteg Suppressive Effect Is Not Specific To Nf-kb P65 Exmentioning

confidence: 99%

“…FhTeg was prepared as previously published (25). Endotoxin levels were determined using the PyroGene Endotoxin Detection System (Cambrex/ Lonza, Walkersville, MD).…”

Section: Animals and Agsmentioning

confidence: 99%

See 3 more Smart Citations

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

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The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

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Evaluation of the Immune Regulatory Properties of Dendritic Cells During Fasciola hepatica Infection

Freire

2020

Methods in Molecular Biology

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TheFasciola hepaticaTegumental Antigen Suppresses Dendritic Cell Maturation and Function

Cited by 106 publications

References 51 publications

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Evaluation of the Immune Regulatory Properties of Dendritic Cells During Fasciola hepatica Infection

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