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Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients

BACKGROUND: Patients with primary immunodeficiency (PID) often suffer from frequent respiratory tract infections. Despite standard treatment with IgG-substitution and antibiotics many patients do not improve significantly. Therefore, we hypothesized that additional immune deficits may be present amo...

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Autores principales: Cederlund, Andreas, Olliver, Marie, Rekha, Rokeya Sultana, Lindh, Monica, Lindbom, Lennart, Normark, Staffan, Henriques-Normark, Birgitta, Andersson, Jan, Agerberth, Birgitta, Bergman, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246483/
https://www.ncbi.nlm.nih.gov/pubmed/22216247
http://dx.doi.org/10.1371/journal.pone.0029316
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author Cederlund, Andreas
Olliver, Marie
Rekha, Rokeya Sultana
Lindh, Monica
Lindbom, Lennart
Normark, Staffan
Henriques-Normark, Birgitta
Andersson, Jan
Agerberth, Birgitta
Bergman, Peter
author_facet Cederlund, Andreas
Olliver, Marie
Rekha, Rokeya Sultana
Lindh, Monica
Lindbom, Lennart
Normark, Staffan
Henriques-Normark, Birgitta
Andersson, Jan
Agerberth, Birgitta
Bergman, Peter
author_sort Cederlund, Andreas
collection PubMed
description BACKGROUND: Patients with primary immunodeficiency (PID) often suffer from frequent respiratory tract infections. Despite standard treatment with IgG-substitution and antibiotics many patients do not improve significantly. Therefore, we hypothesized that additional immune deficits may be present among these patients. OBJECTIVE: To investigate if PID patients exhibit impaired production of antimicrobial peptides (AMPs) in nasal fluid and a possible link between AMP-expression and Th17-cells. METHODS: Nasal fluid, nasopharyngeal swabs and peripheral blood mononuclear cells (PBMCs) were collected from patients and healthy controls. AMP levels were measured in nasal fluid by Western blotting. Nasal swabs were cultured for bacteria. PBMCs were stimulated with antigen and the supernatants were assessed for IL-17A release by ELISA. RESULTS: In healthy controls and most patients, AMP levels in nasal fluid were increased in response to pathogenic bacteria. However, this increase was absent in patients with common variable immunodeficiency (CVID) and Hyper-IgE syndrome (HIES), despite the presence of pathogenic bacteria. Furthermore, stimulation of PBMCs revealed that both HIES and CVID patients exhibited an impaired production of IL-17A. CONCLUSION: CVID and HIES patients appear to have a dysregulated AMP response to pathogenic bacteria in the upper respiratory tract, which could be linked to an aberrant Th17 cell response.
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spelling pubmed-32464832012-01-03 Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients Cederlund, Andreas Olliver, Marie Rekha, Rokeya Sultana Lindh, Monica Lindbom, Lennart Normark, Staffan Henriques-Normark, Birgitta Andersson, Jan Agerberth, Birgitta Bergman, Peter PLoS One Research Article BACKGROUND: Patients with primary immunodeficiency (PID) often suffer from frequent respiratory tract infections. Despite standard treatment with IgG-substitution and antibiotics many patients do not improve significantly. Therefore, we hypothesized that additional immune deficits may be present among these patients. OBJECTIVE: To investigate if PID patients exhibit impaired production of antimicrobial peptides (AMPs) in nasal fluid and a possible link between AMP-expression and Th17-cells. METHODS: Nasal fluid, nasopharyngeal swabs and peripheral blood mononuclear cells (PBMCs) were collected from patients and healthy controls. AMP levels were measured in nasal fluid by Western blotting. Nasal swabs were cultured for bacteria. PBMCs were stimulated with antigen and the supernatants were assessed for IL-17A release by ELISA. RESULTS: In healthy controls and most patients, AMP levels in nasal fluid were increased in response to pathogenic bacteria. However, this increase was absent in patients with common variable immunodeficiency (CVID) and Hyper-IgE syndrome (HIES), despite the presence of pathogenic bacteria. Furthermore, stimulation of PBMCs revealed that both HIES and CVID patients exhibited an impaired production of IL-17A. CONCLUSION: CVID and HIES patients appear to have a dysregulated AMP response to pathogenic bacteria in the upper respiratory tract, which could be linked to an aberrant Th17 cell response. Public Library of Science 2011-12-27 /pmc/articles/PMC3246483/ /pubmed/22216247 http://dx.doi.org/10.1371/journal.pone.0029316 Text en Cederlund 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
Cederlund, Andreas
Olliver, Marie
Rekha, Rokeya Sultana
Lindh, Monica
Lindbom, Lennart
Normark, Staffan
Henriques-Normark, Birgitta
Andersson, Jan
Agerberth, Birgitta
Bergman, Peter
Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title_full Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title_fullStr Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title_full_unstemmed Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title_short Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients
title_sort impaired release of antimicrobial peptides into nasal fluid of hyper-ige and cvid patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246483/
https://www.ncbi.nlm.nih.gov/pubmed/22216247
http://dx.doi.org/10.1371/journal.pone.0029316
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