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.