MyD88 associated ROS generation is crucial for Lactobacillus induced IL-12 production in macrophage

• Published in: PloS one 2012-04, Vol.7 (4), p.e35880-e35880
• Main Authors: Ichikawa, Shintaro, Miyake, Mika, Fujii, Rei, Konishi, Yutaka
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bacteria; Biology; Cells, Cultured; Cytokines; Dendritic cells; Gram-negative bacteria; Host-Pathogen Interactions; Immune response; Immune system; Immunology; Infections; Interleukin 12; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-12 - secretion; Kinases; Lactic acid; Lactic acid bacteria; Lactobacillus; Lactobacillus - immunology; Lactobacillus - physiology; Listeria; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; Macrophages, Peritoneal - secretion; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Mycobacterium avium; Mycobacterium tuberculosis; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; NAD(P)H oxidase; Oxidases; Oxygen; Peritoneum; Phagocytosis; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors; Strains (organisms); TLR2 protein; Toll-like receptors; Toll-Like Receptors - deficiency; Toll-Like Receptors - genetics; Transcription, Genetic; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035880

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.