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Soluble bacterial constituents down-regulate secretion of IL-12 in response to intact Gram-positive bacteria.

Artikel i vetenskaplig tidskrift
Författare Cecilia Barkman
Anna Martner
Christina Hessle
Agnes E Wold
Publicerad i Microbes and infection / Institut Pasteur
Volym 10
Nummer/häfte 14-15
Sidor 1484-93
ISSN 1286-4579
Publiceringsår 2008
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor 1484-93
Språk en
Länkar dx.doi.org/10.1016/j.micinf.2008.08...
Ämnesord IL-12, phagocytosis, cytokines
Ämneskategorier Mikrobiologi, Immunbiologi

Sammanfattning

Intact Gram-positive bacteria induce production of large amounts of IL-12 from freshly isolated human monocytes. Here the bacterial structures and signalling pathways involved were studied and compared with those leading to IL-6 production, and to IL-12 production in response to LPS after IFN-gamma pre-treatment. Intact bifidobacteria induced massive production of IL-12 (1ng/ml) and IL-6 (>30ng/ml) from human PBMC, whereas fragmented bifidobacteria induced IL-6, but no IL-12. IL-12 production induced by intact bifidobacteria was inhibited by pre-treatment with bifidobacterial sonicate, peptidoglycan, muramyl dipeptide, lipoteichoic acid, the soluble TLR2 agonist Pam(3)Cys-SK(4), or anti-TLR2 antibodies. Blocking of phagocytosis by cytochalasin, inhibition of the JNK or NF-kappaB pathways or treatment with Wortmannin also reduced the IL-12 response to intact Gram-positive bacteria. LPS induced moderate levels of IL-12 (0.31ng/ml), but only from IFN-gamma pre-treated PBMC. This IL-12 production was enhanced by Wortmannin and unaffected by blocking the JNK pathway. Thus, intact Gram-positive bacteria trigger monocyte production of large amounts of IL-12 via a distinct pathway that is turned off by fragmented Gram-positive bacteria. This may be a physiological feedback, since such fragments may signal that further activation of the phagocyte via the IL-12/IFN-gamma loop is unnecessary.

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