title: Manipulation of innate immunity by a bacterial secreted peptide: lantibiotic nisin Z is selectively immunomodulatory.
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.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Melissa
authors.initials: M
authors.lastname: Elliott
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nijnik
authors.forename: Laure
authors.initials: L
authors.lastname: Magrangeas-Janot
authors.forename: Mukesh
authors.initials: M
authors.lastname: Pasupuleti
authors.forename: Lisa
authors.initials: L
authors.lastname: Thorson
authors.forename: Shuhua
authors.initials: S
authors.lastname: Ma
authors.forename: Donna M
authors.initials: DM
authors.lastname: Easton
authors.forename: Manjeet
authors.initials: M
authors.lastname: Bains
authors.forename: Brett
authors.initials: B
authors.lastname: Finlay
authors.forename: Eefjan J
authors.initials: EJ
authors.lastname: Breukink
authors.forename: Hans
authors.initials: H
authors.lastname: Georg-Sahl
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D058491:Bacterial Load / Q000528:radiation effects; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D056747:Immunomodulation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009561:Nisin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019779:Salmonella enterica / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha; D009561:Nisin; C071364:nisin Z
keywords: Antimicrobial peptide; immunomodulatory; innate immunity; lantibiotic; nisin