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Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults
BACKGROUND: An increasing number of patients have medical conditions with altered host immunity or that require immunosuppressive medications. While immunosuppression is associated with increased risk of infection, the precise effect of immunosuppression on innate immunity is not well understood. We...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893205/ https://www.ncbi.nlm.nih.gov/pubmed/20596538 http://dx.doi.org/10.1371/journal.pone.0011343 |
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author | Dunne, Dana W. Shaw, Albert Bockenstedt, Linda K. Allore, Heather G. Chen, Shu Malawista, Stephen E. Leng, Lin Mizue, Yuka Piecychna, Marta Zhang, Lin Towle, Virginia Bucala, Richard Montgomery, Ruth R. Fikrig, Erol |
author_facet | Dunne, Dana W. Shaw, Albert Bockenstedt, Linda K. Allore, Heather G. Chen, Shu Malawista, Stephen E. Leng, Lin Mizue, Yuka Piecychna, Marta Zhang, Lin Towle, Virginia Bucala, Richard Montgomery, Ruth R. Fikrig, Erol |
author_sort | Dunne, Dana W. |
collection | PubMed |
description | BACKGROUND: An increasing number of patients have medical conditions with altered host immunity or that require immunosuppressive medications. While immunosuppression is associated with increased risk of infection, the precise effect of immunosuppression on innate immunity is not well understood. We studied monocyte Toll-like receptor (TLR) expression and cytokine production in 137 patients with autoimmune diseases who were maintained on immunosuppressive medications and 419 non-immunosuppressed individuals. METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood monocytes were assessed for surface expression of TLRs 1, 2, and 4. After incubation with TLR agonists, in vitro production of the cytokines IL-8, TNFα, and MIF were measured by ELISA as a measure of TLR signaling efficiency and downstream effector responsiveness. Immunosuppressed patients had significantly higher TLR4 surface expression when compared to non-immunosuppressed adults (TLR4 %-positive 70.12±2.28 vs. 61.72±2.05, p = 0.0008). IL-8 and TNF-α baseline levels did not differ, but were significantly higher in the autoimmune disease group following TLR stimulation. By contrast, baseline MIF levels were elevated in monocytes from immunosuppressed individuals. By multivariable analyses, IL-8 and TNFα, but not MIF levels, were associated with the diagnosis of an underlying autoimmune disease. However, only MIF levels were significantly associated with the use of immunosuppressive medications. CONCLUSIONS/SIGNIFICANCE: Our results reveal that an enhanced innate immune response is a feature of patients with autoimmune diseases treated with immunosuppressive agents. The increased risk for infection evident in this patient group may reflect a dysregulation rather than a simple suppression of innate immunity. |
format | Text |
id | pubmed-2893205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28932052010-07-01 Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults Dunne, Dana W. Shaw, Albert Bockenstedt, Linda K. Allore, Heather G. Chen, Shu Malawista, Stephen E. Leng, Lin Mizue, Yuka Piecychna, Marta Zhang, Lin Towle, Virginia Bucala, Richard Montgomery, Ruth R. Fikrig, Erol PLoS One Research Article BACKGROUND: An increasing number of patients have medical conditions with altered host immunity or that require immunosuppressive medications. While immunosuppression is associated with increased risk of infection, the precise effect of immunosuppression on innate immunity is not well understood. We studied monocyte Toll-like receptor (TLR) expression and cytokine production in 137 patients with autoimmune diseases who were maintained on immunosuppressive medications and 419 non-immunosuppressed individuals. METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood monocytes were assessed for surface expression of TLRs 1, 2, and 4. After incubation with TLR agonists, in vitro production of the cytokines IL-8, TNFα, and MIF were measured by ELISA as a measure of TLR signaling efficiency and downstream effector responsiveness. Immunosuppressed patients had significantly higher TLR4 surface expression when compared to non-immunosuppressed adults (TLR4 %-positive 70.12±2.28 vs. 61.72±2.05, p = 0.0008). IL-8 and TNF-α baseline levels did not differ, but were significantly higher in the autoimmune disease group following TLR stimulation. By contrast, baseline MIF levels were elevated in monocytes from immunosuppressed individuals. By multivariable analyses, IL-8 and TNFα, but not MIF levels, were associated with the diagnosis of an underlying autoimmune disease. However, only MIF levels were significantly associated with the use of immunosuppressive medications. CONCLUSIONS/SIGNIFICANCE: Our results reveal that an enhanced innate immune response is a feature of patients with autoimmune diseases treated with immunosuppressive agents. The increased risk for infection evident in this patient group may reflect a dysregulation rather than a simple suppression of innate immunity. Public Library of Science 2010-06-28 /pmc/articles/PMC2893205/ /pubmed/20596538 http://dx.doi.org/10.1371/journal.pone.0011343 Text en Dunne 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 Dunne, Dana W. Shaw, Albert Bockenstedt, Linda K. Allore, Heather G. Chen, Shu Malawista, Stephen E. Leng, Lin Mizue, Yuka Piecychna, Marta Zhang, Lin Towle, Virginia Bucala, Richard Montgomery, Ruth R. Fikrig, Erol Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title | Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title_full | Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title_fullStr | Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title_full_unstemmed | Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title_short | Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults |
title_sort | increased tlr4 expression and downstream cytokine production in immunosuppressed adults compared to non-immunosuppressed adults |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893205/ https://www.ncbi.nlm.nih.gov/pubmed/20596538 http://dx.doi.org/10.1371/journal.pone.0011343 |
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