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IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis
Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resi...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882833/ https://www.ncbi.nlm.nih.gov/pubmed/20498022 http://dx.doi.org/10.1084/jem.20092265 |
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author | Mittal, Rahul Gonzalez-Gomez, Ignacio Panigrahy, Ashok Goth, Kerstin Bonnet, Richard Prasadarao, Nemani V. |
author_facet | Mittal, Rahul Gonzalez-Gomez, Ignacio Panigrahy, Ashok Goth, Kerstin Bonnet, Richard Prasadarao, Nemani V. |
author_sort | Mittal, Rahul |
collection | PubMed |
description | Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10(−/−) mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis. |
format | Text |
id | pubmed-2882833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28828332010-12-07 IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis Mittal, Rahul Gonzalez-Gomez, Ignacio Panigrahy, Ashok Goth, Kerstin Bonnet, Richard Prasadarao, Nemani V. J Exp Med Article Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10(−/−) mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis. The Rockefeller University Press 2010-06-07 /pmc/articles/PMC2882833/ /pubmed/20498022 http://dx.doi.org/10.1084/jem.20092265 Text en © 2010 Mittal et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Mittal, Rahul Gonzalez-Gomez, Ignacio Panigrahy, Ashok Goth, Kerstin Bonnet, Richard Prasadarao, Nemani V. IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title | IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title_full | IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title_fullStr | IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title_full_unstemmed | IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title_short | IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis |
title_sort | il-10 administration reduces pge-2 levels and promotes cr3-mediated clearance of escherichia coli k1 by phagocytes in meningitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882833/ https://www.ncbi.nlm.nih.gov/pubmed/20498022 http://dx.doi.org/10.1084/jem.20092265 |
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