Immune response to recombinant Burkholderia pseudomallei FliC

Burkholderia pseudomallei is a flagellated Gram-negative bacterium which is the causative agent of melioidosis. The disease poses a major public health problem in tropical regions and diabetes is a major risk factor. The high mortality rate of melioidosis is associated with severe sepsis which invol...

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Autores principales: Koosakulnirand, Sirikamon, Phokrai, Phornpun, Jenjaroen, Kemajittra, Roberts, Rosemary A., Utaisincharoen, Pongsak, Dunachie, Susanna J., Brett, Paul J., Burtnick, Mary N., Chantratita, Narisara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002054/
https://www.ncbi.nlm.nih.gov/pubmed/29902230
http://dx.doi.org/10.1371/journal.pone.0198906
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author Koosakulnirand, Sirikamon
Phokrai, Phornpun
Jenjaroen, Kemajittra
Roberts, Rosemary A.
Utaisincharoen, Pongsak
Dunachie, Susanna J.
Brett, Paul J.
Burtnick, Mary N.
Chantratita, Narisara
author_facet Koosakulnirand, Sirikamon
Phokrai, Phornpun
Jenjaroen, Kemajittra
Roberts, Rosemary A.
Utaisincharoen, Pongsak
Dunachie, Susanna J.
Brett, Paul J.
Burtnick, Mary N.
Chantratita, Narisara
author_sort Koosakulnirand, Sirikamon
collection PubMed
description Burkholderia pseudomallei is a flagellated Gram-negative bacterium which is the causative agent of melioidosis. The disease poses a major public health problem in tropical regions and diabetes is a major risk factor. The high mortality rate of melioidosis is associated with severe sepsis which involves the overwhelming production of pro-inflammatory cytokines. Bacterial flagellar protein (flagellin) activates Toll-like receptor 5 (TLR5)-mediated innate immune signaling pathways and induces adaptive immune response. However, previous studies of TLR5 signaling in melioidosis have been performed using recombinant flagellin from Salmonella Typhimurium instead of B. pseudomallei. This study aimed to investigate human innate immune response and antibody response against a recombinant B. pseudomallei flagellin (rFliC). We prepared B. pseudomallei rFliC and used it to stimulate HEK-Blue(TM)-hTLR5 and THP1-Dual(TM) cells to assess TLR5 activation. Subsequently, whole blood stimulation assays with rFliC were performed ex vivo. TLR5-flagellin interactions trigger activation of transcription factor NF-κB in HEK-Blue(TM)-hTLR5 cells. Pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) productions from whole blood in response to rFliC differed between fourteen healthy individuals. The levels of these cytokines changed in a dose and time-dependent manner. ELISA was used to determine rFliC-specific antibodies in serum samples from different groups of melioidosis patients and healthy subjects. IgG antibody to rFliC in melioidosis patients with diabetes were higher compared with non-diabetic patients. Our results show that B. pseudomallei flagellin is a potent immune stimulator and that the immune responses to rFliC are different among individuals. This may provide valuable insights toward the potential use of rFliC in vaccine development.
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spelling pubmed-60020542018-06-25 Immune response to recombinant Burkholderia pseudomallei FliC Koosakulnirand, Sirikamon Phokrai, Phornpun Jenjaroen, Kemajittra Roberts, Rosemary A. Utaisincharoen, Pongsak Dunachie, Susanna J. Brett, Paul J. Burtnick, Mary N. Chantratita, Narisara PLoS One Research Article Burkholderia pseudomallei is a flagellated Gram-negative bacterium which is the causative agent of melioidosis. The disease poses a major public health problem in tropical regions and diabetes is a major risk factor. The high mortality rate of melioidosis is associated with severe sepsis which involves the overwhelming production of pro-inflammatory cytokines. Bacterial flagellar protein (flagellin) activates Toll-like receptor 5 (TLR5)-mediated innate immune signaling pathways and induces adaptive immune response. However, previous studies of TLR5 signaling in melioidosis have been performed using recombinant flagellin from Salmonella Typhimurium instead of B. pseudomallei. This study aimed to investigate human innate immune response and antibody response against a recombinant B. pseudomallei flagellin (rFliC). We prepared B. pseudomallei rFliC and used it to stimulate HEK-Blue(TM)-hTLR5 and THP1-Dual(TM) cells to assess TLR5 activation. Subsequently, whole blood stimulation assays with rFliC were performed ex vivo. TLR5-flagellin interactions trigger activation of transcription factor NF-κB in HEK-Blue(TM)-hTLR5 cells. Pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) productions from whole blood in response to rFliC differed between fourteen healthy individuals. The levels of these cytokines changed in a dose and time-dependent manner. ELISA was used to determine rFliC-specific antibodies in serum samples from different groups of melioidosis patients and healthy subjects. IgG antibody to rFliC in melioidosis patients with diabetes were higher compared with non-diabetic patients. Our results show that B. pseudomallei flagellin is a potent immune stimulator and that the immune responses to rFliC are different among individuals. This may provide valuable insights toward the potential use of rFliC in vaccine development. Public Library of Science 2018-06-14 /pmc/articles/PMC6002054/ /pubmed/29902230 http://dx.doi.org/10.1371/journal.pone.0198906 Text en © 2018 Koosakulnirand et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Koosakulnirand, Sirikamon
Phokrai, Phornpun
Jenjaroen, Kemajittra
Roberts, Rosemary A.
Utaisincharoen, Pongsak
Dunachie, Susanna J.
Brett, Paul J.
Burtnick, Mary N.
Chantratita, Narisara
Immune response to recombinant Burkholderia pseudomallei FliC
title Immune response to recombinant Burkholderia pseudomallei FliC
title_full Immune response to recombinant Burkholderia pseudomallei FliC
title_fullStr Immune response to recombinant Burkholderia pseudomallei FliC
title_full_unstemmed Immune response to recombinant Burkholderia pseudomallei FliC
title_short Immune response to recombinant Burkholderia pseudomallei FliC
title_sort immune response to recombinant burkholderia pseudomallei flic
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002054/
https://www.ncbi.nlm.nih.gov/pubmed/29902230
http://dx.doi.org/10.1371/journal.pone.0198906
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