IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo

Katherine A Smith, Rick M Maizels

Research output: Contribution to journalArticlepeer-review

Abstract

IL-6 plays a pivotal role in favoring T-cell commitment toward a Th17 cell rather than Treg-cell phenotype, as established through in vitro model systems. We predicted that in the absence of IL-6, mice infected with the gastrointestinal helminth Heligmosomoides polygyrus would show reduced Th17-cell responses, but also enhanced Treg-cell activity and consequently greater susceptibility. Surprisingly, worm expulsion was markedly potentiated in IL-6-deficient mice, with significantly stronger adaptive Th2 responses in both IL-6(-/-) mice and BALB/c recipients of neutralizing anti-IL-6 monoclonal Ab. Although IL-6-deficient mice showed lower steady-state Th17-cell levels, IL-6-independent Th17-cell responses occurred during in vivo infection. We excluded the Th17 response as a factor in protection, as Ab neutralization did not modify immunity to H. polygyrus infection in BALB/c mice. Resistance did correlate with significant changes to the associated Treg-cell phenotype however, as IL-6-deficient mice displayed reduced expression of Foxp3, Helios, and GATA-3, and enhanced production of cytokines within the Treg-cell population. Administration of an anti-IL-2:IL-2 complex boosted Treg-cell proportions in vivo, reduced adaptive Th2 responses to WT levels, and fully restored susceptibility to H. polygyrus in IL-6-deficient mice. Thus, in vivo, IL-6 limits the Th2 response, modifies the Treg-cell phenotype, and promotes host susceptibility following helminth infection.
Original languageEnglish
Pages (from-to)150-61
Number of pages12
JournalEuropean Journal of Immunology
Volume44
Issue number1
Early online date8 Oct 2013
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Animals
  • Antibodies, Blocking
  • Cells, Cultured
  • DNA-Binding Proteins
  • Disease Susceptibility
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • Gene Expression Regulation
  • Interleukin-6
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nematospiroides dubius
  • Parasite Load
  • Phenotype
  • Strongylida Infections
  • T-Lymphocytes, Regulatory
  • Th17 Cells
  • Th2 Cells
  • Transcription Factors

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