Abstract

Nearly one quarter of the world’s population is infected with helminth parasites. A common feature of helminth infections is the manifestation of a type 2 immune response, characterized by T helper 2 (Th2) cells that mediate anti-helminth immunity. In addition, recent literature describes a close association between type 2 immune responses and wound repair, suggesting that a Th2 response may concurrently mediate repair of parasite-induced damage. The molecular mechanisms that govern Th2 responses are poorly understood, although it is clear that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the immune system, play a central role. Here, we review the molecular mechanisms by which DCs polarize Th2 cells, examining both helminth antigens and helminth-mediated tissue damage as Th2-inducing triggers. Finally, we discuss the implication of these findings in the context of metabolic disorders, as recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

Highlights

  • Helminths are parasitic worms that infect one quarter of the world’s population

  • We recently showed that mammalian target of rapamycin (mTOR) is not involved in T helper 2 (Th2) skewing by omega-1- or soluble egg antigens (SEA)-conditioned monocyte-derived dendritic cells (moDCs) [77], the question whether helminths or their products affect glycolytic www.frontiersin.org reprograming in dendritic cells (DCs), and how this relates to Th2 polarization, constitutes an exciting new area of research

  • Supernatants from SEAprimed moDCs do not skew toward Th2 [83], and neither SEAnor omega-1-stimulated bone marrowderived DCs (BMDCs) induce Th2 when separated from CD4+ T cells in transwells [39], indicating that an active polarizing signal in these studies is likely provided by surface molecules

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Summary

Introduction

Helminths are parasitic worms that infect one quarter of the world’s population. They classically evoke strong type 2 immune responses characterized by the induction of T helper 2 (Th2) cells, which secrete cytokines like IL-4, IL-5, and IL-13. It was noted that the NF-κB signaling pathway seems to be involved in Th2 polarization, as SEA- or LNFPIII-stimulated BMDCs from NF-κB1 knockout mice fail to prime a Th2 response [65, 66].

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