IL-1α and inflammasome-independent IL-1β promote neutrophil infiltration following alum vaccination

Ewa Oleszycka, Hannah B T Moran, Graham A Tynan, Claire H Hearnden, Graham Coutts, Matthew Campbell, Stuart M Allan, Christopher J Scott, Ed C Lavelle

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Despite its long record of successful use in human vaccines, the mechanisms underlying the immunomodulatory effects of alum are not fully understood. Alum is a potent inducer of interleukin-1 (IL-1) secretion in vitro in dendritic cells and macrophages via Nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome activation. However, the contribution of IL-1 to alum-induced innate and adaptive immune responses is controversial and the role of IL-1α following alum injection has not been addressed. This study shows that IL-1 is dispensable for alum-induced antibody and CD8 T cell responses to ovalbumin. However, IL-1 is essential for neutrophil infiltration into the injection site, while recruitment of inflammatory monocytes and eosinophils is IL-1 independent. Both IL-1α and IL-1β are released at the site of injection and contribute to the neutrophil response. Surprisingly, these effects are NLRP3-inflammasome independent as is the infiltration of other cell populations. However, while NLRP3 and caspase 1 were dispensable, alum-induced IL-1β at the injection site was dependent on the cysteine protease cathepsin S. Overall, these data demonstrate a previously unreported role for cathepsin S in IL-1β secretion, show that inflammasome formation is dispensable for alum-induced innate immunity and reveal that IL-1α and IL-1β are both necessary for alum-induced neutrophil influx in vivo.

Original languageEnglish
Pages (from-to)9-24
Number of pages16
JournalFEBS journal
Volume283
Issue number1
Early online date07 Oct 2015
DOIs
Publication statusPublished - 11 Jan 2016

Keywords

  • Alum Compounds
  • Animals
  • Inflammasomes
  • Interleukin-1alpha
  • Interleukin-1beta
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration
  • Vaccination

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