IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity

PLoS Pathog. 2013;9(8):e1003531. doi: 10.1371/journal.ppat.1003531. Epub 2013 Aug 1.


Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β(-/-)), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Chronic Disease
  • Immunity, Innate*
  • Immunity, Mucosal*
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology*
  • Interleukin-33
  • Interleukins / genetics
  • Interleukins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nematospiroides dubius / immunology*
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / pathology
  • Th2 Cells / immunology


  • Antirheumatic Agents
  • IL33 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-33
  • Interleukins
  • Mydgf protein, mouse

Grant support

The research leading to these results has received funding from the European community seventh framework program [FP7/2009–2014] under EC-GA no[241642] and part of this work was funded by grants from the Swiss National Science Foundation and the Institute of Arthritis Research. NLH is supported by the Swiss Vaccine Research Institute. KMM is supported by EMBO long-term fellowship and the Australian NHMRC post-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.