Effects of Macrolide Antibiotics on Th1 Cell and Th2 Cell Development Mediated by Langerhans Cells.
- Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or a Th2 immune response. In this study, we investigated the effects of macrolide antibiotics on Th1 cell and Th2 cell development mediated by LCs.


METHODS
LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with each macrolide antibiotic, via the hind footpad. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated using reverse transcriptase polymerase chain reaction.


RESULTS
Injection of OVA peptide-pulsed LDCs, which had been treated with josamycin or spiramycin, inhibited Th2 cell development as represented by down-regulation of interleukin (IL)-4 production as well as Th1 cell development as represented by down-regulation of interferon (IFN)-g production. This inhibition of Th1 cell and Th2 cell development was associated with suppression of CD86 and T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. Furthermore, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to josamycin than to spiramycin.


CONCLUSIONS
These results suggest that topical application of josamycin to AD lesions colonized with S. aureus would be beneficial for control of AD by acting on both superficial S. aureus and epidermal LCs, and inhibiting the development of Th2 cells.
Meiji Pharmaceutical University, Department of Microbial Science and Host Defense, Tokyo, Japan.
Katsuhiko
K
Matsui
Saki
S
Tamai
Reiko
R
Ikeda
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology*; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000900:Anti-Bacterial Agents; D018942:Macrolides