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

Smith, K. A. and Maizels, R. M. (2014) IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo. European Journal of Immunology, 44(1), pp. 150-161. (doi: 10.1002/eji.201343746) (PMID:24185641) (PMCID:PMC3992848)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Smith, K. A., and Maizels, R. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: European Journal of Immunology
• Publisher: Wiley
• ISSN: 0014-2980
• ISSN (Online): 1521-4141
• Published Online: 08 October 2013
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in European Journal of Immunology 44(1):150-161
• Publisher Policy: Reproduced under a Creative Commons license