Manipulation of innate immunity by a bacterial secreted peptide: Lantibiotic nisin Z is selectively immunomodulatory

Jason Kindrachuk, Håvard Jenssen, Melissa Elliott, Anastasia Nijnik, Laure Magrangeas-Janot, Mukesh Pasupuleti, Lisa Thorson, Shuhua Ma, Donna M. Easton, Manjeet Bains, Brett Finlay, Eefjan J. Breukink, Hans Georg-Sahl, Robert Hancock

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Innate immunity is triggered by a variety of bacterial molecules, resulting in both protective and potentially harmful pro-inflammatory responses. Further, innate immunity also provides a mechanism for the maintenance of homeostasis between the host immune system and symbiotic or non-pathogenic microorganisms. However, the bacterial factors that mediate these protective effects have been incompletely defined. Here, it was demonstrated that the lantiobiotic nisin Z is able to modulate host immune responses and mediate protective host immunity. Nisin Z induced the secretion of the chemokines MCP-1, IL-8 and Gro-α, and significantly reduced TNF-α induction in response to bacterial LPS in human PBMC. The results correlated with the ability of nisin Z to confer protection against both the Gram-positive organism Staphylococcus aureus, and the Gram-negatives Salmonella enterica sv. Typhimurium and Escherichia coli in murine challenge models. Mechanistic studies revealed that nisin Z modulates host immunity through similar mechanisms as natural host defense peptides, engaging multiple signal transduction pathways and growth factor receptors. The results presented herein demonstrate that, in addition to nisin Z, other bacterial cationic peptides and, in particular, the lantibiotics, could represent a new class of secreted bacterial molecule with immunomodulatory activities.

Original languageEnglish
Pages (from-to)315-327
Number of pages13
JournalInnate Immunity
Volume19
Issue number3
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Keywords

  • Antimicrobial peptide
  • immunomodulatory
  • innate immunity
  • lantibiotic
  • nisin

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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