Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.

Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the stu...

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Autores principales: Maria J Sanchez-Quintero, Maria J Torres, Ana B Blazquez, Enrique Gómez, Tahia D Fernandez, Inmaculada Doña, Adriana Ariza, Inmaculada Andreu, Lidia Melendez, Miguel Blanca, Cristobalina Mayorga
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/f9730b893ec6480996723edd655e0fce
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spelling oai:doaj.org-article:f9730b893ec6480996723edd655e0fce2021-11-18T08:55:06ZSynergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.1932-620310.1371/journal.pone.0074198https://doaj.org/article/f9730b893ec6480996723edd655e0fce2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24066120/?tool=EBIhttps://doaj.org/toc/1932-6203Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.Maria J Sanchez-QuinteroMaria J TorresAna B BlazquezEnrique GómezTahia D FernandezInmaculada DoñaAdriana ArizaInmaculada AndreuLidia MelendezMiguel BlancaCristobalina MayorgaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74198 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maria J Sanchez-Quintero
Maria J Torres
Ana B Blazquez
Enrique Gómez
Tahia D Fernandez
Inmaculada Doña
Adriana Ariza
Inmaculada Andreu
Lidia Melendez
Miguel Blanca
Cristobalina Mayorga
Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
description Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.
format article
author Maria J Sanchez-Quintero
Maria J Torres
Ana B Blazquez
Enrique Gómez
Tahia D Fernandez
Inmaculada Doña
Adriana Ariza
Inmaculada Andreu
Lidia Melendez
Miguel Blanca
Cristobalina Mayorga
author_facet Maria J Sanchez-Quintero
Maria J Torres
Ana B Blazquez
Enrique Gómez
Tahia D Fernandez
Inmaculada Doña
Adriana Ariza
Inmaculada Andreu
Lidia Melendez
Miguel Blanca
Cristobalina Mayorga
author_sort Maria J Sanchez-Quintero
title Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
title_short Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
title_full Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
title_fullStr Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
title_full_unstemmed Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
title_sort synergistic effect between amoxicillin and tlr ligands on dendritic cells from amoxicillin-delayed allergic patients.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/f9730b893ec6480996723edd655e0fce
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