Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells

Falcón, Cristián; Carranza, Franco; Martínez, Fernando F.; Knubel, Carolina Paola; Masih, Diana T.; Motrán, Claudia Cristina; Cervi, Laura

doi:10.1016/j.vetimm.2010.04.007

Cited by 75 publications

(73 citation statements)

References 47 publications

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“…However, this question is still to be solved since BOMAC cells retain properties of ingestion of opsonised bacteria (Jolly et al 2011) which indicates their phagocytic character. Bone marrow derived mouse dendritic cells do not change secretion of IL-6, 10, 12p70, TNF-α upon stimulation with Fh-ES, but they release significant lower amounts of those cytokines upon stimulation with LPS and Fh-ES than stimulated with LPS only (Falcón et al 2010). This was also confirmed in this paper by BOMA cell line for TNF-α secretion.…”

Section: Discussionsupporting

confidence: 85%

“…We noted that LPS activated BOMA cells release lower amounts of TNF-α after Fh-ES stimulation. Fh-ES impairs the activation of dendritic cells (DC) induced by TLR ligands (Falcón et al 2010), but the lack of a change of IL-4 and IFN-γ or TNF-α during our experiments might be caused by a non-physiological behavior of BOMAC cells, due to an absence of response observed to LPS. However, this question is still to be solved since BOMAC cells retain properties of ingestion of opsonised bacteria (Jolly et al 2011) which indicates their phagocytic character.…”

Section: Discussionmentioning

confidence: 65%

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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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 65%

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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“…With only a few exceptions [24], extracts of helminth parasites have not consistently been shown to increase expression of markers of maturation DCs [16,25]. Exposure to HD antigens enhanced MHC II and CD80 expression on DCs, indicating a semimature activation state that has the capacity to interact with naïve and effector T cells and drive immunological responses.…”

Section: Discussionmentioning

confidence: 99%

Adoptive transfer of helminth antigen‐pulsed dendritic cells protects against the development of experimental colitis in mice

et al. 2015

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Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO),Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionOver the last three generations there has been a substantial rise in the incidence and prevalence of inflammatory disease especially in developed nations, but also in developing countries [1]. As autoimmune, inflammatory, and idiopathic diseases (e.g. inflammatory bowel disease [IBD]) emerge as global threats, and with awareness Correspondence: Dr. Derek M. McKay e-mail: dmckay@ucalgary.ca of the shortcomings of current therapies for these chronic debilitating conditions, there is a pressing need to advance knowledge of novel means to treat and ultimately cure inflammatory disease. Amongst many potential candidates, infection with helminth parasites has generated considerable interest because the host response to these parasites involves a range of endogenous immunoregulatory events. Infection with helminth parasites is a potent stimulus on the mammalian immune system, with remarkable commonality between mice and humans [2]. Furthermore, helminths are not mere passive victims of the host immune response; they C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3126-3139 Immunomodulation 3127 have evolved multiple means to circumvent the host's anti-worm response [3]. Consequently, it was postulated that infection with parasitic helminths could ameliorate concomitant disease. Preclinical murine experimentation, case reports, and small clinical trials have demonstrated that infection with helminths reduces the severity of inflammatory disease [4][5][6][7], via a variety of mechanisms such as mobilization of regulatory T (Treg) and B (Breg) cells and the synthesis of .As an alternative to infection with viable helminth parasites, systemic administration of crude extracts of a variety of helminth parasites has been shown to inhibit inflammation, including colitis [9][10][11]. However, to date, it has proven challenging to isolate pure single bioactive molecules from helminth parasites [12][13][14] that could serve as new drugs: indeed, a combination of helminthderived molecules may be required to effectively suppress immune activity and protect against immunopathology/inflammatory disease.Expanding upon the evidence that infection with helminth parasites or treatment with worm extracts inhibit inflammation, one can hypothesize that priming a specific immune regulatory or effector cell in vit...

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“…A variety of Treg differentiation models demonstrated the necessity of IL-10 secretion by tolerogenic DCs for tolerance induction (39)(40)(41)(42) and for the maintenance of suppressive Tregs upon strong inflammatory signals (9,(42)(43)(44). Like PSMa peptides, Candida albicans, Cryptococcus neoformans, and Fasciola hepatica subvert the immune system by promoting DC tolerogenicity and Treg differentiation (9,(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

PSM Peptides of Staphylococcus aureus Activate the p38–CREB Pathway in Dendritic Cells, Thereby Modulating Cytokine Production and T Cell Priming

Armbruster

Richardson

Schreiner

et al. 2016

The Journal of Immunology

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The challenging human pathogen Staphylococcus aureus has highly efficient immune evasion strategies for causing a wide range of diseases, from skin and soft tissue to life-threatening infections. Phenol-soluble modulin (PSM) peptides are major pathogenicity factors of community-associated methicillin-resistant S. aureus strains. In previous work, we demonstrated that PSMs in combination with TLR2 ligand from S. aureus induce tolerogenic dendritic cells (DCs) characterized by the production of high amounts of IL-10, but no proinflammatory cytokines. This in turn promotes the activation of regulatory T cells while impairing Th1 response; however, the signaling pathways modulated by PSMs remain elusive. In this study, we analyzed the effects of PSMs on signaling pathway modulation downstream of TLR2. TLR2 stimulation in combination with PSMα3 led to increased and prolonged phosphorylation of NF-κB, ERK, p38, and CREB in mouse bone marrow–derived DCs compared with single TLR2 activation. Furthermore, inhibition of p38 and downstream MSK1 prevented IL-10 production, which in turn reduced the capacity of DCs to activate regulatory T cells. Interestingly, the modulation of the signaling pathways by PSMs was independent of the known receptor for PSMs, as shown by experiments with DCs lacking the formyl peptide receptor 2. Instead, PSMs penetrate the cell membrane most likely by transient pore formation. Moreover, colocalization of PSMs and p38 was observed near the plasma membrane in the cytosol, indicating a direct interaction. Thus, PSMs from S. aureus directly modulate the signaling pathway p38–CREB in DCs, thereby impairing cytokine production and in consequence T cell priming to increase the tolerance toward the pathogen.

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Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells

Cited by 75 publications

References 47 publications

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

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

Adoptive transfer of helminth antigen‐pulsed dendritic cells protects against the development of experimental colitis in mice

PSM Peptides of Staphylococcus aureus Activate the p38–CREB Pathway in Dendritic Cells, Thereby Modulating Cytokine Production and T Cell Priming

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