title: MyD88 associated ROS generation is crucial for Lactobacillus induced IL-12 production in macrophage.
abstract: It is well known that some strains of lactic acid bacteria (LAB) can induce IL-12 which plays an important role in modulating immune responses. However, the mechanisms by which LAB induce IL-12 production remain unclear. Here, we examine the role of toll-like receptors (TLR's) and reactive oxygen species (ROS) in IL-12 production by LAB stimulated peritoneal macrophages. Our results indicate that a TLR is not necessary for IL-12 induction by LAB, whilst the universal adaptor protein, MyD88, is essential. Specific strains of LAB induced ROS that correlated with both the frequency of phagocytosis and IL-12 production. Reduction in IL-12 production by NADPH oxidase inhibitors or ROS scavengers demonstrates the crucial role of ROS in IL-12 induction. Interestingly, deficiency of TLR2, 4, 9 or MyD88 did not affect the phagocytosis of LAB strain KW3110, a potent IL-12 inducer, and ROS production was significantly reduced only in MyD88 deficient macrophages. These results suggest the existence of TLR-MyD88 independent LAB recognition and MyD88 related ROS induction mechanisms. We show here the importance of ROS for IL-12 induction and provide new insights into IL-12 induction by LAB.
authors.affiliation: Central Laboratories for Frontier Technology, Kirin Holdings Co., Ltd., Yokohama, Japan. Shintaro_Ichikawa@kirin.co.jp
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Mika
authors.initials: M
authors.lastname: Miyake
authors.forename: Rei
authors.initials: R
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007778:Lactobacillus / Q000276:immunology / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D018664:Interleukin-12