Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands: involvement of mast cells and dendritic cells.
BACKGROUND
It has been suggested that airway bacterial infections exacerbate allergic disorders, and bacterial components in the air affect allergic inflammation via Toll-like receptors expressed on mast cells and dendritic cells in the airway mucosa.


OBJECTIVE
Peptidoglycan (PGN) is a major component of the bacterial cell wall. We investigated the effect of PGN on the effector phase of allergic inflammation, in comparison with the effect of CpG-oligodeoxynucleotides (CpG), which is known to be a Th1 adjuvant.


METHODS
Ovalbumin (OVA)-sensitized mice were challenged intranasally with OVA alone or OVA together with PGN or CpG. Nasal allergic symptoms and eosinophilia were scored, and the OVA-specific cytokine response was examined in the cells of cervical lymph nodes and nasal mucosa. Bone marrow-derived mast cells (BMMCs) and dendritic cells (BMDCs) were stimulated with PGN or CpG in vitro, and the expression level of cytokines and chemokines was examined by RT-PCR. In addition, the expression level of chemokines was examined by RT-PCR in mast cells of OVA-sensitized mice challenged with OVA alone or OVA together with PGN or CpG.


RESULTS
PGN exposure exacerbated the nasal allergic symptoms and eosinophilia, whereas CpG exposure suppressed them. In addition, PGN exposure increased the OVA-specific IL-4 response in the cells, whereas CpG exposure decreased it. On the other hand, there were no significant differences in the OVA-specific IFN-gamma response. PGN but not CpG induced the expression of thymus and activation-regulated chemokine (TARC) and macrophage/monocyte-derived chemokine (MDC) in both BMMCs and mast cells of mice sensitized and challenged with OVA. CpG but not PGN induced the expression of IFN-beta and interferon-inducible protein-10 (IP-10) in BMDCs, and histamine did not influence this effect.


CONCLUSIONS
These results demonstrate that PGN exposure exacerbates allergic inflammation mainly via mast cells, whereas CpG exposure suppresses allergic inflammation mainly via dendritic cells.
Yamamoto
K
K
Department of Microbiology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. yamakazu@mb.med.kyoto-u.ac.jp
Kawamura
I
I
Ito
J
J
Mitsuyama
M
M
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D010457:Peptidoglycan / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology
D000942:Antigens, Bacterial; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D015847:Interleukin-4; D010047:Ovalbumin