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Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia

Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wi...

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Autores principales: Bhan, Urvashi, Ballinger, Megan N., Zeng, Xianying, Newstead, Michael J., Cornicelli, Matthew D., Standiford, Theodore J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845620/
https://www.ncbi.nlm.nih.gov/pubmed/20360853
http://dx.doi.org/10.1371/journal.pone.0009896
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author Bhan, Urvashi
Ballinger, Megan N.
Zeng, Xianying
Newstead, Michael J.
Cornicelli, Matthew D.
Standiford, Theodore J.
author_facet Bhan, Urvashi
Ballinger, Megan N.
Zeng, Xianying
Newstead, Michael J.
Cornicelli, Matthew D.
Standiford, Theodore J.
author_sort Bhan, Urvashi
collection PubMed
description Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4(lps-d)), mice deficient in TLR9 (TLR9(−/−)) and TLR4/9 double mutant mice (TLR4(lps-d)/TLR9(−/−)) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4(lps-d)/TLR9(−/−) double mutant mice. Early lung expression of TNF-α, IL-12, and chemokines was TLR4 dependent, while IFN-γ production and the later expression of TNF-α and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4(lps-d)/TLR9(−/−) double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.
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spelling pubmed-28456202010-04-02 Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia Bhan, Urvashi Ballinger, Megan N. Zeng, Xianying Newstead, Michael J. Cornicelli, Matthew D. Standiford, Theodore J. PLoS One Research Article Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4(lps-d)), mice deficient in TLR9 (TLR9(−/−)) and TLR4/9 double mutant mice (TLR4(lps-d)/TLR9(−/−)) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4(lps-d)/TLR9(−/−) double mutant mice. Early lung expression of TNF-α, IL-12, and chemokines was TLR4 dependent, while IFN-γ production and the later expression of TNF-α and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4(lps-d)/TLR9(−/−) double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response. Public Library of Science 2010-03-26 /pmc/articles/PMC2845620/ /pubmed/20360853 http://dx.doi.org/10.1371/journal.pone.0009896 Text en Bhan 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhan, Urvashi
Ballinger, Megan N.
Zeng, Xianying
Newstead, Michael J.
Cornicelli, Matthew D.
Standiford, Theodore J.
Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title_full Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title_fullStr Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title_full_unstemmed Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title_short Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia
title_sort cooperative interactions between tlr4 and tlr9 regulate interleukin 23 and 17 production in a murine model of gram negative bacterial pneumonia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845620/
https://www.ncbi.nlm.nih.gov/pubmed/20360853
http://dx.doi.org/10.1371/journal.pone.0009896
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