Mycobacteria Bypass Mucosal NF-kB Signalling to Induce an Epithelial Anti-Inflammatory IL-22 and IL-10 Response.

Summary, in English

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: Nataliya Lutay; Gisela Håkansson; Nader Alaridah; Oskar Hallgren; Gunilla Westergren-Thorsson; Gabriela Godaly
• Department/s: Dermatology and Venereology (Lund); Clinical Microbiology, Malmö; Infection Medicine (BMC); Lung Biology; Respiratory Medicine, Allergology, and Palliative Medicine
• Publishing year: 2014
• Language: English
• Publication/Series: PLoS ONE
• Volume: 9
• Issue: 1
• Full text: - 962 kB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/24489729?dopt=Abstract; http://dx.doi.org/10.1371/journal.pone.0086466
• Document type: Journal article
• Publisher: Public Library of Science (PLoS)
• Topic: Infectious Medicine; Microbiology in the medical area; Respiratory Medicine and Allergy
• Status: Published
• Research group: Clinical Microbiology, Malmö; Lung Biology
• ISBN/ISSN/Other: ISSN: 1932-6203