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Induction and regulation of pathogenic Th17 cell responses in schistosomiasis

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Abstract

Schistosomiasis is a major tropical disease caused by trematode helminths in which the host mounts a pathogenic immune response against tissue-trapped parasite eggs. The immunopathology consists of egg antigen-specific CD4 T cell-mediated granulomatous inflammation that varies greatly in magnitude in humans and among mouse strains in an experimental model. New evidence, covered in this review, intimately ties the development of severe pathology to IL-17-producing CD4 T helper (Th17) cells, a finding that adds a new dimension to the traditional CD4 Th1 vs. Th2 cell paradigm. Most examined mouse strains, in fact, develop severe immunopathology with substantial Th17 as well as Th1 and Th2 cell responses; a solely Th2-polarized response is an exception that is only observed in low-pathology strains such as the C57BL/6. The ability to mount pathogenic Th17 cell responses is genetically determined and depends on the production of IL-23 and IL-1β by antigen presenting cells following recognition of egg antigens; analyses of several F2 progenies of (high × low)-pathology strain crosses demonstrated that quantitative trait loci governing IL-17 levels and disease severity vary substantially from cross to cross. Low pathology is dominant, which may explain the low incidence of severe disease in humans; however, coinfection with intestinal nematodes can also dampen pathogenic Th17 cell responses by promoting regulatory mechanisms such as those afforded by alternatively activated macrophages and T regulatory cells. A better understanding of the pathways conducive to severe forms of schistosomiasis and their regulation should lead to interventions similar to those presently used to manage other immune-mediated diseases.

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Acknowledgment

This work was supported by the National Institutes of Health grant R01-18919 to MJS. The authors declare no financial conflicts of interest.

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  1. Department of Pathology, Tufts University School of Medicine, Boston, MA, USA

    Bridget M. Larkin, Patrick M. Smith, Holly E. Ponichtera, Mara G. Shainheit, Laura I. Rutitzky & Miguel J. Stadecker

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  1. Bridget M. Larkin
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  2. Patrick M. Smith
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  3. Holly E. Ponichtera
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  4. Mara G. Shainheit
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  5. Laura I. Rutitzky
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  6. Miguel J. Stadecker
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Correspondence to Miguel J. Stadecker.

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This article is a contribution to the special issue on Immunoparasitology - Guest Editor: Miguel J. Stadecker

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Larkin, B.M., Smith, P.M., Ponichtera, H.E. et al. Induction and regulation of pathogenic Th17 cell responses in schistosomiasis. Semin Immunopathol 34, 873–888 (2012). https://doi.org/10.1007/s00281-012-0341-9

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