title: Lactobacillus gasseri OLL2809 and its RNA suppress proliferation of CD4(+) T cells through a MyD88-dependent signalling pathway.
abstract: Recent studies have shown that probiotics are beneficial in prevention and improvement of inflammatory diseases. Accumulating evidence indicates that probiotics can modulate immune cell responses, although the specific molecular mechanism by which probiotics work remains elusive. Because T cells express receptors for microbial components, we examined whether the probiotic strain Lactobacillus gasseri OLL2809 (LG2809) and its components regulate murine CD4(+) T-cell activation. LG2809, as well as two other Lactobacillus strains, inhibited proliferation of CD4(+) T cells; LG2809 had the strongest suppressive activity among them. RNA isolated from LG2809 was also shown to have suppressive activity. We observed this suppressive effect in the culture of CD4(+) T cells stimulated with anti-CD3/CD28 treatment, suggesting a direct effect on CD4(+) T cells. In contrast, the suppressive effect was not observed for CD4(+) T cells from myeloid differentiation primary response gene 88 (MyD88) protein-deficient mice, and was abrogated in the presence of an anti-oxidant reagent, N-acetyl-cysteine (NAC). These results demonstrate that the suppressive effect of LG2809 and its RNA occurred through a MyD88-dependent signalling pathway and suggest involvement of a reactive oxygen species-dependent mechanism. LG2809 RNA injected subcutaneously suppressed delayed-type-hypersensitivity response in DO11.10 mice, and the suppression was abrogated by treatment with NAC. Collectively, these results suggest that suppression of T-cell proliferation by RNA may be one of the mechanisms when a probiotic bacterial strain exerts suppressive effects on inflammatory responses.
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, France.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamada
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sashihara
authors.forename: Shuuji
authors.initials: S
authors.lastname: Ikegami
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Totsuka
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D007778:Lactobacillus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012329:RNA, Bacterial; D017382:Reactive Oxygen Species