Identification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance

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TY  - JOUR
  - O'Carroll, C,Fagan, A,Shanahan, F,Carmody, RJ
  - 2014
  - January
  - Journal of immunology (Baltimore, Md. : 1950)
  - Identification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance
  - Validated
  - WOS: 35 ()
  - TOLL-LIKE RECEPTORS NF-KAPPA-B ENDOTOXIN TOLERANCE NEGATIVE REGULATION CYTOKINE PRODUCTION GENE-EXPRESSION INNATE IMMUNITY KUPFFER CELL IRAK-M ACTIVATION
  - 192
  - 427
  - 436
  - LPS tolerance is an essential immune-homeostatic response to repeated exposure to LPS that prevents excessive inflammatory responses. LPS tolerance induces a state of altered responsiveness in macrophages, resulting in repression of proinflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, we analyzed the transcriptional plasticity of macrophages following LPS tolerance using genome-wide transcriptional profiling. We demonstrate that LPS tolerance is a transient state and that the expression of proinflammatory genes is restored to levels comparable to the acute response to LPS. However, following recovery from LPS tolerance a number of genes remained locked in a tolerizable state, including IL-33, CD86, IL-10, and NFIL3. Furthermore, we identified of a number of genes uniquely induced following recovery from LPS tolerance. Thus, macrophages adopt a unique transcriptional profile following recovery from LPS tolerance and have a distinct expression pattern of regulators of Ag presentation, antiviral responses, and transcription factors. Our data suggest that recovery from LPS tolerance leads to a hybrid macrophage activation state that is proinflammatory and microbicidal in nature but that possesses a regulatory anti-inflammatory profile distinct from that of LPS-tolerant and LPS-activated macrophages.
  - 10.4049/jimmunol.1301722
DA  - 2014/01
ER  - 
@article{V243941770,
   = {O'Carroll,  C and Fagan,  A and Shanahan,  F and Carmody,  RJ },
   = {2014},
   = {January},
   = {Journal of immunology (Baltimore, Md. : 1950)},
   = {Identification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance},
   = {Validated},
   = {WOS: 35 ()},
   = {TOLL-LIKE RECEPTORS NF-KAPPA-B ENDOTOXIN TOLERANCE NEGATIVE REGULATION CYTOKINE PRODUCTION GENE-EXPRESSION INNATE IMMUNITY KUPFFER CELL IRAK-M ACTIVATION},
   = {192},
  pages = {427--436},
   = {{LPS tolerance is an essential immune-homeostatic response to repeated exposure to LPS that prevents excessive inflammatory responses. LPS tolerance induces a state of altered responsiveness in macrophages, resulting in repression of proinflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, we analyzed the transcriptional plasticity of macrophages following LPS tolerance using genome-wide transcriptional profiling. We demonstrate that LPS tolerance is a transient state and that the expression of proinflammatory genes is restored to levels comparable to the acute response to LPS. However, following recovery from LPS tolerance a number of genes remained locked in a tolerizable state, including IL-33, CD86, IL-10, and NFIL3. Furthermore, we identified of a number of genes uniquely induced following recovery from LPS tolerance. Thus, macrophages adopt a unique transcriptional profile following recovery from LPS tolerance and have a distinct expression pattern of regulators of Ag presentation, antiviral responses, and transcription factors. Our data suggest that recovery from LPS tolerance leads to a hybrid macrophage activation state that is proinflammatory and microbicidal in nature but that possesses a regulatory anti-inflammatory profile distinct from that of LPS-tolerant and LPS-activated macrophages.}},
   = {10.4049/jimmunol.1301722},
  source = {IRIS}
}
AUTHORSO'Carroll, C,Fagan, A,Shanahan, F,Carmody, RJ
YEAR2014
MONTHJanuary
JOURNAL_CODEJournal of immunology (Baltimore, Md. : 1950)
TITLEIdentification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance
STATUSValidated
TIMES_CITEDWOS: 35 ()
SEARCH_KEYWORDTOLL-LIKE RECEPTORS NF-KAPPA-B ENDOTOXIN TOLERANCE NEGATIVE REGULATION CYTOKINE PRODUCTION GENE-EXPRESSION INNATE IMMUNITY KUPFFER CELL IRAK-M ACTIVATION
VOLUME192
ISSUE
START_PAGE427
END_PAGE436
ABSTRACTLPS tolerance is an essential immune-homeostatic response to repeated exposure to LPS that prevents excessive inflammatory responses. LPS tolerance induces a state of altered responsiveness in macrophages, resulting in repression of proinflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, we analyzed the transcriptional plasticity of macrophages following LPS tolerance using genome-wide transcriptional profiling. We demonstrate that LPS tolerance is a transient state and that the expression of proinflammatory genes is restored to levels comparable to the acute response to LPS. However, following recovery from LPS tolerance a number of genes remained locked in a tolerizable state, including IL-33, CD86, IL-10, and NFIL3. Furthermore, we identified of a number of genes uniquely induced following recovery from LPS tolerance. Thus, macrophages adopt a unique transcriptional profile following recovery from LPS tolerance and have a distinct expression pattern of regulators of Ag presentation, antiviral responses, and transcription factors. Our data suggest that recovery from LPS tolerance leads to a hybrid macrophage activation state that is proinflammatory and microbicidal in nature but that possesses a regulatory anti-inflammatory profile distinct from that of LPS-tolerant and LPS-activated macrophages.
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ISBN_ISSN
EDITION
URL
DOI_LINK10.4049/jimmunol.1301722
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