Peptidoglycan from Staphylococcus aureus induces T(H)2 immune response in mice.

BACKGROUND AND OBJECTIVE Atopic dermatitis patients have an increased number of type 2 helper (T(H)2) cells in their peripheral blood and superficial Staphylococcus aureus colonization. The purpose of this study was to clarify the effects of peptidoglycan (PEG) from S aureus on the induction of the TH2 immune response in mice. METHODS Mice were primed with PEG- and ovalbumin (OVA)-pulsed Langerhans cells (LCs) and given a booster OVA injection 2 days later via the hind footpad. Five days later, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). IL-12 production from cultured LCs was detected by ELISA and Western blot analysis. RESULTS Administration of PEG- and OVA-pulsed LCs into the hind footpads of the mice induced a T(H)2-prone immune response as represented by the enhanced interleukin (IL) 4 expression in the lymph nodes. We further showed that higher levels of IL-12 p40 production by PEG-stimulated LCs relative to IL-12 p70 (p35/p40) production were associated with the induction of the T(H)2 immune response.The LC-derived IL-12 p40 protein induced by PEG stimulation was detected mainly as monomeric and homodimeric IL-12 p40 subunits; other heterodimers including the L-12 p40 subunit, such as IL-23, were undetected. CONCLUSION These results suggest that PEG may have the ability to induce the development of T(H)2 cells through insufficient production of IL-12 p70 and excessive production by LCs of homodimeric IL-12 p40, a known antagonist of bioactive IL-12 p70, offering a possible explanation for the role of S aureus colonization in patients with atopic dermatitis.