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Signaling mediated by toll-Like receptor 5 sensing of pseudomonas aeruginosa flagellin influences IL-1β and IL-18 production by primary fibroblasts derived from the human cornea

Signaling mediated by toll-Like receptor 5 sensing of pseudomonas aeruginosa flagellin influences IL-1β and IL-18 production by primary fibroblasts derived from the human cornea
Signaling mediated by toll-Like receptor 5 sensing of pseudomonas aeruginosa flagellin influences IL-1β and IL-18 production by primary fibroblasts derived from the human cornea
Pseudomonas aeruginosa is the principal cause of bacterial keratitis worldwide and overstimulation of the innate immune system by this organism is believed to contribute significantly to sight loss. In the current study, we have used primary human corneal fibroblast (hCF) cells as an ex vivo model of corneal infection to examine the role of P. aeruginosa flagellum and type three secretion system (TTSS) in inducing inflammasome-associated molecules that trigger IL-1β and IL-18 production during the early stages of the infection. Our results show that P. aeruginosa infection stimulated the non-canonical pathway for IL-1β and IL-18 expression and pathway stimulation was influenced predominantly by the flagellum. Both IL-1β and IL-18 cytokines were expressed intracellularly during bacterial infection, but only the former was released and detected in the extracellular environment. We also investigated the signaling pathways in hCFs mediated by Toll-Like Receptor (TLR)4 and TLR5 sensing of P. aeruginosa, and our data show that the signal triggered by TLR5-flagellin sensing significantly contributed to IL-1β and IL-18 cytokine production in our model. Our study suggests that IL-18 expression is wholly dependent on extracellular flagellin sensing by TLR5, whereas IL-1β expression is also influenced by P. aeruginosa lipopolysacharide. Additionally, we demonstrate that IL-1β and IL-18 production by hCFs can be triggered by both MyD88-dependent and -independent pathways. Overall, our study provides a rationale for the development of targeted therapies, by proposing an inhibition of flagellin-PRR-signaling interactions, in order to ameliorate the inflammatory response characteristic of P. aeruginosa keratitis.
1-13
del Mar Cendra, Maria
150d34a4-4598-4138-96c0-06f3f338cca2
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51
del Mar Cendra, Maria
150d34a4-4598-4138-96c0-06f3f338cca2
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51

del Mar Cendra, Maria, Christodoulides, Myron and Hossain, Parwez (2017) Signaling mediated by toll-Like receptor 5 sensing of pseudomonas aeruginosa flagellin influences IL-1β and IL-18 production by primary fibroblasts derived from the human cornea. Frontiers in Cellular and Infection Microbiology, 7, 1-13, [130]. (doi:10.3389/fcimb.2017.00130).

Record type: Article

Abstract

Pseudomonas aeruginosa is the principal cause of bacterial keratitis worldwide and overstimulation of the innate immune system by this organism is believed to contribute significantly to sight loss. In the current study, we have used primary human corneal fibroblast (hCF) cells as an ex vivo model of corneal infection to examine the role of P. aeruginosa flagellum and type three secretion system (TTSS) in inducing inflammasome-associated molecules that trigger IL-1β and IL-18 production during the early stages of the infection. Our results show that P. aeruginosa infection stimulated the non-canonical pathway for IL-1β and IL-18 expression and pathway stimulation was influenced predominantly by the flagellum. Both IL-1β and IL-18 cytokines were expressed intracellularly during bacterial infection, but only the former was released and detected in the extracellular environment. We also investigated the signaling pathways in hCFs mediated by Toll-Like Receptor (TLR)4 and TLR5 sensing of P. aeruginosa, and our data show that the signal triggered by TLR5-flagellin sensing significantly contributed to IL-1β and IL-18 cytokine production in our model. Our study suggests that IL-18 expression is wholly dependent on extracellular flagellin sensing by TLR5, whereas IL-1β expression is also influenced by P. aeruginosa lipopolysacharide. Additionally, we demonstrate that IL-1β and IL-18 production by hCFs can be triggered by both MyD88-dependent and -independent pathways. Overall, our study provides a rationale for the development of targeted therapies, by proposing an inhibition of flagellin-PRR-signaling interactions, in order to ameliorate the inflammatory response characteristic of P. aeruginosa keratitis.

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fcimb-07-00130 - Version of Record
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Accepted/In Press date: 29 March 2017
Published date: 19 April 2017
Organisations: Clinical & Experimental Sciences, Tissue Infection & Repair

Identifiers

Local EPrints ID: 407976
URI: http://eprints.soton.ac.uk/id/eprint/407976
PURE UUID: 1fb12196-4f50-4d9a-9e56-5fffdf98a1e5
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731
ORCID for Parwez Hossain: ORCID iD orcid.org/0000-0002-3131-2395

Catalogue record

Date deposited: 06 May 2017 01:01
Last modified: 16 Mar 2024 03:48

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Contributors

Author: Maria del Mar Cendra
Author: Parwez Hossain ORCID iD

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