title: Listeriolysin O, a cytolysin derived from Listeria monocytogenes, inhibits generation of ovalbumin-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells.
abstract: Listeriolysin O (LLO), a cholesterol-dependent cytolysin derived from Listeria monocytogenes, is a potent inducer of interleukin (IL)-12, IL-18 and interferon (IFN)-gamma. We have shown that LLO facilitates development of T cells mediating protective immunity against L. monocytogenes through the induction of IFN-gamma production at an early stage. Based on this finding, it is postulated that LLO inhibits differentiation of Th2 cells and the Th2 immune response. By using a murine model of ovalbumin (OVA)-induced allergic rhinitis, we investigated whether LLO has an ability to modulate the Th2-type immune disorder. In mice sensitized intraperitoneally with ovalbumin (OVA)/alum and challenged intranasally with OVA, a large number of eosinophils migrated into the nasal tissue, and high titres of anti-OVA IgE and IgG(1) antibodies were detected in sera. However, LLO treatment during sensitization markedly inhibited the eosinophil infiltration and production of these anti-OVA antibodies. A large number of T cells from mice sensitized and challenged with OVA produced high level of IL-4 and IL-5 but not IFN-gamma after stimulation with OVA. In contrast, OVA-specific IFN-gamma-producing T cells were preferentially induced in mice treated with LLO at the time of sensitization. In the absence of LLO administration, the expression level of GATA-3 and SOCS-3 in CD4(+) T cells was enhanced after sensitization with OVA. LLO treatment resulted in a reduction of GATA-3 and SOCS-3 expressions but induced the transcription of T-bet instead. Taken together, these data show clearly that LLO is capable of inhibiting Th2 immune response by skewing differentiation of antigen-specific T cells into Th1 cells.
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Kawamura
authors.forename: T
authors.initials: T
authors.lastname: Tominaga
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: C
authors.initials: C
authors.lastname: Kohda
authors.forename: J
authors.initials: J
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Mitsuyama
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000627:therapeutic use; D006460:Hemolysin Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012220:Rhinitis / Q000276:immunology / Q000517:prevention & control*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000098815:T-bet Transcription Factor
chemical_list: D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma; D010047:Ovalbumin; C038705:hlyA protein, Listeria monocytogenes