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Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype

Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether...

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Autores principales: Xie, Qi, Brackenbury, Louise S., Hill, Darryl J., Williams, Neil A., Qu, Xun, Virji, Mumtaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944954/
https://www.ncbi.nlm.nih.gov/pubmed/24599281
http://dx.doi.org/10.1371/journal.pone.0090999
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author Xie, Qi
Brackenbury, Louise S.
Hill, Darryl J.
Williams, Neil A.
Qu, Xun
Virji, Mumtaz
author_facet Xie, Qi
Brackenbury, Louise S.
Hill, Darryl J.
Williams, Neil A.
Qu, Xun
Virji, Mumtaz
author_sort Xie, Qi
collection PubMed
description Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether Moraxella catarrhalis Ubiquitous Surface Protein A1 (UspA1), known to bind to a widely expressed human cell surface receptor CEACAM1, influences monocyte differentiation as receptor engagement has been shown to have profound effects on monocytes. We used the recombinant molecules corresponding to the regions of UspA1 which either bind (rD-7; UspA1(527–665)) or do not bind (r6–8; UspA1(659–863)) to CEACAM1 and investigated their effects on CD206, CD80 and CD86 expression on freshly isolated human CD14+ monocytes from peripheral blood mononuclear cells (PBMC). Exposure to rD-7, but not r6–8, biased monocyte differentiation towards a CD14+CD206+ phenotype, with reduced CD80 expression. Monocytes treated with rD-7 also secreted high levels of IL-1ra and chemokine IL-8 but not IL-10 or IL-12p70. The effects of rD-7 were independent of any residual endotoxin. Unexpectedly, these effects of rD-7 were also independent of its ability to bind to CEACAM1, as monocyte pre-treatment with the anti-CEACAM antibody A0115 known to inhibit rD-7 binding to the receptor, did not affect rD-7-driven differentiation. Further, another control protein rD-7/D (a mutant form of rD-7, known not to bind to CEACAMs), also behaved as the parent molecule. Our data suggest that specific regions of M. catarrhalis adhesin UspA1 may modulate inflammation during infection through a yet unknown receptor on monocytes.
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spelling pubmed-39449542014-03-10 Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype Xie, Qi Brackenbury, Louise S. Hill, Darryl J. Williams, Neil A. Qu, Xun Virji, Mumtaz PLoS One Research Article Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether Moraxella catarrhalis Ubiquitous Surface Protein A1 (UspA1), known to bind to a widely expressed human cell surface receptor CEACAM1, influences monocyte differentiation as receptor engagement has been shown to have profound effects on monocytes. We used the recombinant molecules corresponding to the regions of UspA1 which either bind (rD-7; UspA1(527–665)) or do not bind (r6–8; UspA1(659–863)) to CEACAM1 and investigated their effects on CD206, CD80 and CD86 expression on freshly isolated human CD14+ monocytes from peripheral blood mononuclear cells (PBMC). Exposure to rD-7, but not r6–8, biased monocyte differentiation towards a CD14+CD206+ phenotype, with reduced CD80 expression. Monocytes treated with rD-7 also secreted high levels of IL-1ra and chemokine IL-8 but not IL-10 or IL-12p70. The effects of rD-7 were independent of any residual endotoxin. Unexpectedly, these effects of rD-7 were also independent of its ability to bind to CEACAM1, as monocyte pre-treatment with the anti-CEACAM antibody A0115 known to inhibit rD-7 binding to the receptor, did not affect rD-7-driven differentiation. Further, another control protein rD-7/D (a mutant form of rD-7, known not to bind to CEACAMs), also behaved as the parent molecule. Our data suggest that specific regions of M. catarrhalis adhesin UspA1 may modulate inflammation during infection through a yet unknown receptor on monocytes. Public Library of Science 2014-03-05 /pmc/articles/PMC3944954/ /pubmed/24599281 http://dx.doi.org/10.1371/journal.pone.0090999 Text en © 2014 Xie 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
Xie, Qi
Brackenbury, Louise S.
Hill, Darryl J.
Williams, Neil A.
Qu, Xun
Virji, Mumtaz
Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title_full Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title_fullStr Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title_full_unstemmed Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title_short Moraxella catarrhalis Adhesin UspA1-derived Recombinant Fragment rD-7 Induces Monocyte Differentiation to CD14+CD206+ Phenotype
title_sort moraxella catarrhalis adhesin uspa1-derived recombinant fragment rd-7 induces monocyte differentiation to cd14+cd206+ phenotype
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944954/
https://www.ncbi.nlm.nih.gov/pubmed/24599281
http://dx.doi.org/10.1371/journal.pone.0090999
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