Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice.
Listeriolysin O (LLO) derived from Listeria monocytogenes is highly capable of inducing interleukin (IL)-12, IL-18 and interferon (IFN)-gamma, and facilitates the generation of Th1 cells. We have recently shown that recombinant LLO (rLLO) inhibits generation of ovalbumin (OVA)-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells. In the present study, we investigated the effect of rLLO on the effector phase of Th2-dependent allergic rhinitis in BALB/c mice sensitized with OVA. In mice sensitized intraperitoneally and challenged intranasally with OVA, nasal allergic symptoms such as sneezing and nose-scratching were observed at a high frequency. A high titre of anti-OVA IgE antibody was detected in sera and a large number of eosinophils migrated into the nasal tissue. However, rLLO treatment during the intranasal challenge inhibited the allergic symptoms, production of anti-OVA IgE antibody and eosinophil infiltration. Though rLLO did not affect antigen-specific cytokine production from splenic CD4(+) T cells, rLLO significantly suppressed OVA-specific IL-4 and IL-5 production from nasal mononuclear cells. We further found that rLLO inhibited the recruitment of CD4(+) T cells in nasal mucosa, and diminished the transcription and cell surface expression of CCR4 on splenic CD4(+) T cells. Moreover, rLLO was able to inhibit the passive cutaneous anaphylaxis reaction mediated by anaphylactic antibodies (IgE and IgG(1)) and mast cells. Taken together, these data showed that rLLO suppresses the effector phase of allergic rhinitis by inhibition of Th2 cell recruitment to nasal mucosa and type I allergic reaction.
Yamamoto
K
K
Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kawamura
I
I
Tominaga
T
T
Nomura
T
T
Ito
J
J
Mitsuyama
M
M
D000818:Animals; D001427:Bacterial Toxins / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000627:therapeutic use*; D006460:Hemolysin Proteins; D018928:Immunity, Mucosal / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D012220:Rhinitis / Q000276:immunology / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology
D001427:Bacterial Toxins; C515355:Ccr4 protein, mouse; D016207:Cytokines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D018664:Interleukin-12; D010047:Ovalbumin; C038705:hlyA protein, Listeria monocytogenes