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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway.

M G Cleveland, J D Gorham, T L Murphy, E Tuomanen, K M Murphy
M G Cleveland
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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J D Gorham
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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T L Murphy
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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E Tuomanen
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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K M Murphy
Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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ABSTRACT

Interleukin 12 (IL-12) strongly augments gamma interferon production by natural killer (NK) and T cells. IL-12 also promotes effective cell-mediated immune responses, which are particularly important against intracellular bacteria such as Listeria monocytogenes. While the lipopolysaccharide (LPS) of gram-negative bacteria induces monocyte production of IL-12, the relevant gram-positive components which induce IL-12 production are uncharacterized. We used the human monocytic cell line THP-1 to study IL-12 induction by gram-positive bacteria. Muramyl dipeptides as well as the major muramyl tetrapeptide component of Streptococcus pneumoniae were inactive for inducing IL-12. In contrast, lipoteichoic acid (LTA), a predominant surface glycolipid of gram-positive bacteria, potently induced IL-12 p40 gene expression. A competitive LPS antagonist, Rhodobacter sphaeroides LPS, inhibited LTA-induced IL-12 production, suggesting a common pathway for LPS and LTA in IL-12 activation. Pretreatment of cells with anti-CD14 monoclonal antibody blocked both LPS and LTA induction of IL-12 p40 expression. LTA also induced Thl development in naive CD4 T cells by an IL-12-dependent mechanism, indicating direct induction of physiologic levels of IL-12. Together, these results show that LTA is a potent surface structure of gram-positive bacteria which induces IL-12 in monocytes through a CD14-mediated pathway.

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Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway.
M G Cleveland, J D Gorham, T L Murphy, E Tuomanen, K M Murphy
Infection and Immunity Jun 1996, 64 (6) 1906-1912; DOI:

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Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway.
M G Cleveland, J D Gorham, T L Murphy, E Tuomanen, K M Murphy
Infection and Immunity Jun 1996, 64 (6) 1906-1912; DOI:
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