T cells in helminth infection: the regulators and the regulated

Taylor, Matthew J.; Werf, Nienke van der; Maizels, Rick M.

doi:10.1016/j.it.2012.01.001

Cited by 150 publications

(148 citation statements)

References 82 publications

(154 reference statements)

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“…In the absence of appropriate regulation, Th2 responses can cause destruction not only to the parasite, but also to host tissue, and cause pathology. The mechanisms by which Tregs restrain the activation and proliferation of other cells are me-diated both by cell-cell interactions and by soluble factors [96]. Helminths induce the generation and expansion of Tregs, and enhance Treg function by inducing the expression of negative costimulatory molecules such as CTLA-4 and anti-inflammatory cytokines, including IL-10 and TGF-β.…”

Section: Immunity To Helminthesmentioning

confidence: 99%

Helminth Infection and Type 1 Diabetes

Zaccone¹,

Hall²

2012

Rev Diabet Stud

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■ AbstractThe increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our coevolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.

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Section: Immunity To Helminthesmentioning

confidence: 99%

Helminth Infection and Type 1 Diabetes

Zaccone¹,

Hall²

2012

Rev Diabet Stud

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“…Helminth 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.…”

Section: Introductionmentioning

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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“…We hypothesize that the most important site of immunity to A. suum is the small intestine. Lymph nodes draining the small intestine were expected to contain regulatory T cells and cytokine-secreting T cells (e.g., Th1, Th2, Th17, follicular helper T cells) which had been activated by antigen-presenting cells (Zhu et al 2010;Taylor et al 2012). Such antigenpresenting cells would present A. suum antigens produced in the small intestine.…”

Section: Disscussionmentioning

confidence: 99%

“…These cytokines and other signalling molecules activate a number of other cells, e.g., eosinophils, mast cells, basophils, epithelial cells and smooth muscle cells (Anthony et al 2007). More recent studies have shown that the immune response during helminth infection is regulated by a network of immunosuppressive regulatory T cells (T regs ) and suppressive cytokines like TGF-β and IL-10 (Taylor et al 2012). Resistance, i.e., the Per Skallerup et al 142 ability to suppress establishment and/or subsequent development of infection (Albers et al 1987), is under genetic control by the host (Wakelin 1975).…”

Section: Introductionmentioning

confidence: 99%