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Neisseria lactamica attenuates TLR-1/2-induced cytokine responses in nasopharyngeal epithelial cells using PPAR

Neisseria lactamica attenuates TLR-1/2-induced cytokine responses in nasopharyngeal epithelial cells using PPAR
Neisseria lactamica attenuates TLR-1/2-induced cytokine responses in nasopharyngeal epithelial cells using PPAR
The upper respiratory tract commensal Neisseria lactamica (Nlac) induces protective humoral immunity against pathogenic Nmen serogroup B (Nmen), but whether it also affords anti-inflammatory mucosal protection, as reported for several gut commensals, has not been investigated. Here we demonstrate for the first time that Nlac weakly induces inflammatory responses compared with Nmen in the nasopharyngeal epithelial cell line, Detroit 562, and that Nlac achieves this by attenuation of secretory cytokine (TNF-? and IL-6) and to a lesser extent chemokine (IL-8 and RANTES) responses. Culture of Detroit cells with Nlac inhibited the induction of cytokine-chemokine mRNA by Nmen, reduced Nmen-induced NF-?? activity and increased constitutive PPAR-? protein expression. Pretreatment of Detroit cells with a PPAR-? antagonist abrogated the attenuation of inflammatory IL-6 by Nlac, as did heat-killing of the organisms and preventing their invasion with cytochalasin D. Inflammatory responses from Detroit cells were readily attenuated by Nlac following stimulation with pathogenic Nmen but more specifically following stimulation with the TLR-1/2 agonist Pam3Cys and pro-inflammatory cytokines (IL-1?, TNF-?) but not LTA or LPS. These results indicate that Nlac plays an important role in suppressing pathogen-induced inflammation in the nasopharyngeal mucosa, mediated through TLR-1/2 stimulation, by activating PPAR-? and inhibiting NF-?? activity.

1462-5814
554-568
Tezera, L.
c5598dbf-23a8-4934-96a4-7c783bf9e776
Hampton, J.
99197b2c-4db1-4add-a399-1babc53dd722
Jackson, S.K.
6697bd09-3721-4919-9be3-312324bb9b43
Davenport, V.
e56378c5-a008-4565-9826-4181aaaeeffc
Tezera, L.
c5598dbf-23a8-4934-96a4-7c783bf9e776
Hampton, J.
99197b2c-4db1-4add-a399-1babc53dd722
Jackson, S.K.
6697bd09-3721-4919-9be3-312324bb9b43
Davenport, V.
e56378c5-a008-4565-9826-4181aaaeeffc

Tezera, L., Hampton, J., Jackson, S.K. and Davenport, V. (2011) Neisseria lactamica attenuates TLR-1/2-induced cytokine responses in nasopharyngeal epithelial cells using PPAR. Cellular Microbiology, 13 (4), 554-568. (doi:10.1111/j.1462-5822.2010.01554.x).

Record type: Article

Abstract

The upper respiratory tract commensal Neisseria lactamica (Nlac) induces protective humoral immunity against pathogenic Nmen serogroup B (Nmen), but whether it also affords anti-inflammatory mucosal protection, as reported for several gut commensals, has not been investigated. Here we demonstrate for the first time that Nlac weakly induces inflammatory responses compared with Nmen in the nasopharyngeal epithelial cell line, Detroit 562, and that Nlac achieves this by attenuation of secretory cytokine (TNF-? and IL-6) and to a lesser extent chemokine (IL-8 and RANTES) responses. Culture of Detroit cells with Nlac inhibited the induction of cytokine-chemokine mRNA by Nmen, reduced Nmen-induced NF-?? activity and increased constitutive PPAR-? protein expression. Pretreatment of Detroit cells with a PPAR-? antagonist abrogated the attenuation of inflammatory IL-6 by Nlac, as did heat-killing of the organisms and preventing their invasion with cytochalasin D. Inflammatory responses from Detroit cells were readily attenuated by Nlac following stimulation with pathogenic Nmen but more specifically following stimulation with the TLR-1/2 agonist Pam3Cys and pro-inflammatory cytokines (IL-1?, TNF-?) but not LTA or LPS. These results indicate that Nlac plays an important role in suppressing pathogen-induced inflammation in the nasopharyngeal mucosa, mediated through TLR-1/2 stimulation, by activating PPAR-? and inhibiting NF-?? activity.

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More information

e-pub ahead of print date: December 2010
Published date: April 2011
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 353874
URI: http://eprints.soton.ac.uk/id/eprint/353874
ISSN: 1462-5814
PURE UUID: f37f10b5-5208-4208-a209-6289e9708440
ORCID for L. Tezera: ORCID iD orcid.org/0000-0002-7898-6709

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Date deposited: 24 Jun 2013 10:18
Last modified: 20 Jul 2019 00:40

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Contributors

Author: L. Tezera ORCID iD
Author: J. Hampton
Author: S.K. Jackson
Author: V. Davenport

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