Adjuvant effect of lipopolysaccharide on the induction of contact hypersensitivity to haptens in mice

BackgroundToll-like receptor (TLR) 4 is a critical receptor and signal transducer for lipopolysaccharide (LPS), a major component of Gram-negative bacteria. The MyD88-independent pathway downstream of TLR4 leads to functional dendritic cell (DC) maturation, although LPS-induced cytokine production from DCs is MyD88-dependent.ObjectivesWe investigated whether intracutaneously injected LPS alters the functions of cutaneous DCs, leading to enhanced contact hypersensitivity (CH).MethodsThe ear swelling response was measured to evaluate the magnitude of CH. Cell proliferation of allogeneic splenocytes stimulated by DC-enriched draining lymph node (LN) cells was measured by performing a [3H]-thymidine incorporation assay. Epidermal I-A+ cells were evaluated under an epifluorescent microscope. I-A+ FITC-bearing cells from the draining LNs 24 h after FITC application were analyzed on FACScan.ResultsLPS augmented CH induction in C3H/HeN (HeN) and MyD88-knockout (KO) mice but not in C3H/HeJ (HeJ) and H-2Sd-bearing strains such as BALB/c mice. LPS failed to augment the allo-stimulatory ability of DCs in the draining LNs after hapten applications. LPS altered the density and morphology of epidermal I-A+ cell in HeN and BALB/c mice but not in TLR4-deficient HeJ mice. LPS increased the proportion of I-A+ FITC-bearing cells in the LNs 24 h after FITC application in HeN, but not in BALB/c and HeJ.ConclusionsLPS augments the ability of DCs to migrate to the draining LNs, leading to enhanced CH via a TLR4-dependent, MyD88-independent pathway. The different effects of LPS on CH in some strains of mice may explain individual differences in the susceptibility to establish CH to daily antigen exposures in clinical settings.