Mishra, P.K., Patel, N., Wu, W., Bleich, D. & Gause, W.C. Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response. Mucosal Immunol. 6, 297-308

Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
Mucosal Immunology (Impact Factor: 7.54). 07/2012; 6(2). DOI: 10.1038/mi.2012.71
Source: PubMed

ABSTRACT Helminth infection can prevent type 1 diabetes (T1D); however, the regulatory mechanisms inhibiting disease remain largely undefined. In these studies, nonobese diabetic (NOD) IL-4(-/-) mice were infected with the strictly enteric nematode parasite, Heligmosomoides polygyrus. Short-term infection, 5-7 weeks of age, inhibited T1D onset, as late as 40 weeks of age. CD4(+) T-cell STAT6 phosphorylation was inhibited, while suppressed signal transducer and activator of transcription 1 phosphorylation was sustained, as were increases in FOXP3(-), CD4(+) T-cell interleukin (IL)-10 production. Blockade of IL-10 signaling in NOD-IL-4(-/-), but not in NOD, mice during this short interval abrogated protective effects resulting in pancreatic β-cell destruction and ultimately T1D. Transfer of CD4(+) T cells from H. polygyrus (Hp)-inoculated NOD IL-4(-/-) mice to NOD mice blocked the onset of T1D. These studies indicate that Hp infection induces non-T-regulatory cells to produce IL-10 independently of STAT6 signaling and that in this Th2-deficient environment IL-10 is essential for T1D inhibition.Mucosal Immunology advance online publication 18 July 2012. doi:10.1038/mi.2012.71.

Download full-text


Available from: Pankaj K Mishra, Aug 25, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The 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 co-evolution 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.
    The Review of Diabetic Studies 01/2012; 9(4):272-286. DOI:10.1900/RDS.2012.9.272
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 1 diabetes is increasing dramatically in incidence in the developed world. While there may be several reasons for this, improved sanitation and public health measures have altered our interactions with certain infectious agents such as helminths. There is increasing interest in the use of helminths or their products to alleviate inflammatory or allergic conditions. Using rodent models of diabetes, it has been possible to explore the therapeutic potential of both live infections as well as helminth-derived products on the development of autoimmunity. This review provides an overview of the findings from animal models and additionally explores the potential for translation to the clinic.
    International journal for parasitology 01/2013; 43(3-4). DOI:10.1016/j.ijpara.2012.12.004 · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance.
    Nature Reviews Immunology 07/2013; 13(8). DOI:10.1038/nri3476 · 33.84 Impact Factor
Show more