RT Journal Article T1 Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients. A1 Sanchez-Quintero, Maria J A1 Torres, Maria J A1 Blazquez, Ana B A1 Gómez, Enrique A1 Fernandez, Tahia D A1 Doña, Inmaculada A1 Ariza, Adriana A1 Andreu, Inmaculada A1 Melendez, Lidia A1 Blanca, Miguel A1 Mayorga, Cristobalina K1 Amoxicilina K1 Células dendríticas K1 Ligandos K1 Sinergismo medicamentoso K1 Hipersensibilidad retardada K1 Linfocitos K1 Citocinas K1 Exantema K1 Humanos AB 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. PB Public Library of Science YR 2013 FD 2013-09-16 LK http://hdl.handle.net/10668/1377 UL http://hdl.handle.net/10668/1377 LA en NO Sanchez-Quintero MJ, Torres MJ, Blazquez AB, Gómez E, Fernandez TD, Doña I, et al. Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients. PLoS ONE. 2013; 8(9):e74198 NO Journal Article; DS RISalud RD Apr 12, 2025