<i>Schistosoma mansoni</i> Worms Induce Anergy of T Cells via Selective Up-Regulation of Programmed Death Ligand 1 on Macrophages

Smith, Philip; Walsh, Caroline; Mangan, Niamh E.; Fallon, Rosie E.; Sayers, Jon R.; McKenzie, Andrew N. J.; Fallon, Padraic G.

doi:10.4049/jimmunol.173.2.1240

Cited by 177 publications

(170 citation statements)

References 58 publications

(44 reference statements)

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“…Recent studies suggest that these cell surface molecules may be important in macrophagemediated T cell suppression. In particular, PD-L1 expressed by macrophages following S. mansoni infection can trigger T cell anergy in vitro following interactions with PD-1 [37].…”

Section: Control Of Inflammationmentioning

confidence: 99%

Alternatively activated macrophages in helminth infections

Kreider

Anthony

Urban

et al. 2007

Current Opinion in Immunology

312

270

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Section: Control Of Inflammationmentioning

confidence: 99%

Alternatively activated macrophages in helminth infections

Kreider

Anthony

Urban

et al. 2007

Current Opinion in Immunology

312

270

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“…We have developed a model of short term in vitro culture of distinct cell populations with live worms (18). Spleen cells from a naive mouse were cultured with 15 live worms in Transwells for 48 h at 37°C.…”

Section: Passive Transfer Of In Vivo or In Vitro Modulated B Cellsmentioning

confidence: 99%

“…Adult worms were cultured as previously described (18). In brief, adult schistosome worms were obtained 8 wk postinfection by portal perfusion as previously described (24).…”

Section: In Vitro Worm Culturementioning

confidence: 99%

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Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Mangan

Fallon

Smith³

et al. 2004

The Journal of Immunology

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Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses.

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“…Similar to CTLA4, its enhanced expression supports our finding that FhTeg induces anergenic like T cells. In other studies PD1 and its ligand PD-L1 has been shown to play a role in T-cell hyporesponsiveness seen during S. mansoni infection [12,31] and also was elevated during filariasis [13,29] . PD1 expression is also associated with T-cell exhaustion [32], which is mostly centered on CD8 + T cells.…”

mentioning

confidence: 99%

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

Aldridge

O’Neill

2016

Eur J Immunol

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FoxP3 + Treg cells and anergic T cells are the two regulatory phenotypes of T-cell responses associated with helminth infection. Here, we examine the T-cell responses in mice duringKeywords: Anergy r C-type lectin receptors r Dendritic cells r Helminth infection r Host-pathogen interactions r Mannose receptor r T-cell responses Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHelminth parasites can survive within their hosts for many years by suppressing T-cell driven protective immune responses and Th1/Th2-mediated pathology through the induction of regulatory networks that suppress inflammatory responses [1][2][3][4]. These regulatory networks include regulatory T cells (Treg) that in the context of helminth infection is widely understood. Treg cells supCorrespondence: Dr. Sandra M. O'Neill e-mail: sandra.oneill@dcu.ie press the immune response to helminth-driven Th1/Th2 immune pathology through the induction of IL-10 and TGF-β. Brugia malayi, infection induces a regulatory response with enhanced FoxP3 expression and increased cell surface expression of CTLA4, a negative regulator of T-cell function [5] while Schistosoma haematobium infection in humans has also been associated with FoxP3 + Treg cells with the highest percentage of this cell population observed in younger patients [6]. However, less is currently known about the regulatory response termed in vivo anergy or adaptive tolerance.Few studies have examined the role of anergenic T cells during helminth infection. The induction of this cell population is thought C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 1180-1192 Immunity to infection 1181 to be the result of the persistent contact of parasite antigen with immune cells during chronic helminth infection [7]. Anergenic T cells differ from Treg cells in that they do not express FoxP3 or produce IL-10 or TGF-β. Instead anergy is a hyporesponsive state with the failure of T cells to proliferate or produce cytokines when restimulated with antigens in vitro [8]. Anergic T cells do not secrete IL-2, a factor important for T-cell proliferation and effector responses. However, the addition of IL-2 can overcome this hyporesponsiveness, restoring helminth-driven T-cell responses. Gene analysis studies have identified a number of genes including Rnf128 (Grail), Itch, Egr2 and Egr3, and CblB that are involved in the induction and maintenance of T-cell anergy [9,10]. A number of helminth infections have shown T-cell anergy or Tcell hyporesponsiveness to be involved in immune suppression. Studies involving S. mansoni show the enhanced expression of GRAIL is linked to the suppression of Th2 cells and also using a filarial nematode, CD4 + T cells become functionally unresponsive [11,12]. Other studies indicate that anergenic-like T cells are the result of helminth infections, with an increase in anergenic markers and T-cell suppression [13][14][15][16]. Fasciola hepatica causes chronic liver d...

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Schistosoma mansoni Worms Induce Anergy of T Cells via Selective Up-Regulation of Programmed Death Ligand 1 on Macrophages

Cited by 177 publications

References 58 publications

Alternatively activated macrophages in helminth infections

Alternatively activated macrophages in helminth infections

Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

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