Mycobacteria Bypass Mucosal NF-kB Signalling to Induce an Epithelial Anti-Inflammatory IL-22 and IL-10 Response.
Lutay, Nataliya LU ; Håkansson, Gisela LU ; Alaridah, Nader LU ; Hallgren, Oskar LU ; Westergren-Thorsson, Gunilla LU and Godaly, Gabriela LU
(2014)
In PLoS ONE
9(1).
- Abstract
- The mechanisms by which mycobacteria subvert the inflammatory defence to establish chronic infection remain an unresolved question in the pathogenesis of tuberculosis. Using primary epithelial cells, we have analysed mycobacteria induced epithelial signalling pathways from activation of TLRs to cytokine secretion. Mycobacterium bovis bacilli Calmette-Guerin induced phosphorylation of glycogen synthase kinase (GSK)3 by PI3K-Akt in the signalling pathway downstream of TLR2 and TLR4. Mycobacteria did not supress NF-κB by activating the peroxisome proliferator-activated receptor γ. Instead the pro-inflammatory NF-κB was bypassed by mycobacteria induced GSK3 inhibition that promoted the anti-inflammatory transcription factor CREB. Mycobacterial... (More)
- The mechanisms by which mycobacteria subvert the inflammatory defence to establish chronic infection remain an unresolved question in the pathogenesis of tuberculosis. Using primary epithelial cells, we have analysed mycobacteria induced epithelial signalling pathways from activation of TLRs to cytokine secretion. Mycobacterium bovis bacilli Calmette-Guerin induced phosphorylation of glycogen synthase kinase (GSK)3 by PI3K-Akt in the signalling pathway downstream of TLR2 and TLR4. Mycobacteria did not supress NF-κB by activating the peroxisome proliferator-activated receptor γ. Instead the pro-inflammatory NF-κB was bypassed by mycobacteria induced GSK3 inhibition that promoted the anti-inflammatory transcription factor CREB. Mycobacterial infection did not thus induce mucosal pro-inflammatory response as measured by TNFα and IFNγ secretion, but led to an anti-inflammatory IL-10 and IL-22 production. Apart from CREB, MAP3Ks p38 and ERK1/2 activated the transcription factor AP-1 leading to IL-6 production. Interestingly, blocking of TLR4 before infection decreased epithelial IL-6 secretion, but increased the CREB-activated IL-10 production. Our data indicate that mycobacteria supress epithelial pro-inflammatory production by supressing NF-κB activation thereby shifting the infection towards an anti-inflammatory state. This balance between the host immune response and the pathogen could determine the outcome of infection. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4335838
- author
- Lutay, Nataliya
LU
; Håkansson, Gisela
LU
; Alaridah, Nader
LU
; Hallgren, Oskar
LU
; Westergren-Thorsson, Gunilla
LU
and Godaly, Gabriela
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 9
- issue
- 1
- article number
- e86466
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:24489729
- wos:000330510000052
- scopus:84900307196
- pmid:24489729
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0086466
- language
- English
- LU publication?
- yes
- id
- 3378cdb3-f016-431f-acae-85001a96c60e (old id 4335838)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24489729?dopt=Abstract
- date added to LUP
- 2016-04-04 09:25:09
- date last changed
- 2023-09-05 23:10:42
@article{3378cdb3-f016-431f-acae-85001a96c60e,
abstract = {{The mechanisms by which mycobacteria subvert the inflammatory defence to establish chronic infection remain an unresolved question in the pathogenesis of tuberculosis. Using primary epithelial cells, we have analysed mycobacteria induced epithelial signalling pathways from activation of TLRs to cytokine secretion. Mycobacterium bovis bacilli Calmette-Guerin induced phosphorylation of glycogen synthase kinase (GSK)3 by PI3K-Akt in the signalling pathway downstream of TLR2 and TLR4. Mycobacteria did not supress NF-κB by activating the peroxisome proliferator-activated receptor γ. Instead the pro-inflammatory NF-κB was bypassed by mycobacteria induced GSK3 inhibition that promoted the anti-inflammatory transcription factor CREB. Mycobacterial infection did not thus induce mucosal pro-inflammatory response as measured by TNFα and IFNγ secretion, but led to an anti-inflammatory IL-10 and IL-22 production. Apart from CREB, MAP3Ks p38 and ERK1/2 activated the transcription factor AP-1 leading to IL-6 production. Interestingly, blocking of TLR4 before infection decreased epithelial IL-6 secretion, but increased the CREB-activated IL-10 production. Our data indicate that mycobacteria supress epithelial pro-inflammatory production by supressing NF-κB activation thereby shifting the infection towards an anti-inflammatory state. This balance between the host immune response and the pathogen could determine the outcome of infection.}},
author = {{Lutay, Nataliya and Håkansson, Gisela and Alaridah, Nader and Hallgren, Oskar and Westergren-Thorsson, Gunilla and Godaly, Gabriela}},
issn = {{1932-6203}},
language = {{eng}},
number = {{1}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Mycobacteria Bypass Mucosal NF-kB Signalling to Induce an Epithelial Anti-Inflammatory IL-22 and IL-10 Response.}},
url = {{https://lup.lub.lu.se/search/files/5319099/4693299.pdf}},
doi = {{10.1371/journal.pone.0086466}},
volume = {{9}},
year = {{2014}},
}