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Innate immune responses after airway epithelial stimulation with Mycobacterium bovis Bacille-Calmette Guérin

Tenland, Erik LU ; Håkansson, Gisela; Alaridah, Nader LU ; Lutay, Nataliya LU ; Rönnholm, Anna LU ; Hallgren, Oskar LU ; Westergren-Thorsson, Gunilla LU and Godaly, Gabriela LU (2016) In PLoS ONE 11(10).
Abstract

Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells. BCG stimulation specifically reduced neutrophil IL-17RA and epithelial IL-17RE expression. BCG... (More)

Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells. BCG stimulation specifically reduced neutrophil IL-17RA and epithelial IL-17RE expression. BCG induced neutrophil extracellular traps (NETs), but did not have an effect on apoptosis as measured by transcription factor forkhead box O3 (FOXO3). BCG stimulation of AECs induced CXCL8 secretion and neutrophil endothelial passage towards infected epithelia. Infected epithelial cells and neutrophils were not found to be a source of IL-17 cytokines or the interstitial collagenase MMP-1. However, the addition of IFNγ or IL-17A to BCG stimulated primary epithelial cells increased epithelial IL-6 secretion, while the presence of IFNγ reduced neutrophil recruitment. Using our model of mucosal infection we revealed that BCG induces selective mucosal innate immune responses that could lead to induction of vaccine-mediated protection of the lung.

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publication status
published
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in
PLoS ONE
volume
11
issue
10
publisher
Public Library of Science
external identifiers
  • scopus:84991490775
  • wos:000385504100059
ISSN
1932-6203
DOI
10.1371/journal.pone.0164431
language
English
LU publication?
yes
id
bcf1f3a2-5863-4b01-98c3-3ad8b20fa591
date added to LUP
2016-11-01 09:50:32
date last changed
2017-08-13 04:59:48
@article{bcf1f3a2-5863-4b01-98c3-3ad8b20fa591,
  abstract     = {<p>Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells. BCG stimulation specifically reduced neutrophil IL-17RA and epithelial IL-17RE expression. BCG induced neutrophil extracellular traps (NETs), but did not have an effect on apoptosis as measured by transcription factor forkhead box O3 (FOXO3). BCG stimulation of AECs induced CXCL8 secretion and neutrophil endothelial passage towards infected epithelia. Infected epithelial cells and neutrophils were not found to be a source of IL-17 cytokines or the interstitial collagenase MMP-1. However, the addition of IFNγ or IL-17A to BCG stimulated primary epithelial cells increased epithelial IL-6 secretion, while the presence of IFNγ reduced neutrophil recruitment. Using our model of mucosal infection we revealed that BCG induces selective mucosal innate immune responses that could lead to induction of vaccine-mediated protection of the lung.</p>},
  articleno    = {e0164431},
  author       = {Tenland, Erik and Håkansson, Gisela and Alaridah, Nader and Lutay, Nataliya and Rönnholm, Anna and Hallgren, Oskar and Westergren-Thorsson, Gunilla and Godaly, Gabriela},
  issn         = {1932-6203},
  language     = {eng},
  month        = {10},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Innate immune responses after airway epithelial stimulation with Mycobacterium bovis Bacille-Calmette Guérin},
  url          = {http://dx.doi.org/10.1371/journal.pone.0164431},
  volume       = {11},
  year         = {2016},
}