Abstract |
Host defense against many invading Gram-negative bacteria (GNB) depends on innate immune recognition of endotoxin ( lipopolysaccharides, LPS), unique surface glycolipids of GNB. Host responses to endotoxin must be highly sensitive but self-limited. In mammals, optimal sensitivity is achieved by ordered interactions of endotoxin with several different extracellular and cell surface proteins-the LPS-binding protein (LBP), CD14, MD-2, and Toll-like receptor (TLR) 4-reflecting the requirement for specific protein- endotoxin and protein- protein interactions. This complex reaction pathway also provides many ways to attenuate endotoxin-driven inflammation and can explain how differences in endotoxin structure, either intrinsic among GNB or induced by metabolic remodeling, can alter host responsiveness and thus the outcome of host-GNB interactions. Major goals of our research are to better understand: (1) the structural bases of specific host- endotoxin interactions; (2) functional diversity among host endotoxin-binding proteins; and (3) how the actions of various endotoxin-binding proteins are regulated to permit optimal host responses to GNB infection. In addition, the identification of a water-soluble endotoxin:MD-2 complex that, depending on the structure of endotoxin or MD-2, has potent TLR4 agonist or antagonist properties suggests novel pharmacologic approaches to immuno-modulation.
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Authors | Theresa L Gioannini, Jerrold P Weiss |
Journal | Immunologic research
(Immunol Res)
Vol. 39
Issue 1-3
Pg. 249-60
( 2007)
ISSN: 0257-277X [Print] United States |
PMID | 17917069
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
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Chemical References |
- Endotoxins
- Lipopolysaccharide Receptors
- Lipopolysaccharides
- Lymphocyte Antigen 96
- Membrane Proteins
- Toll-Like Receptors
- endotoxin binding proteins
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Topics |
- Animals
- Endotoxins
(immunology, metabolism)
- Gram-Negative Bacteria
(immunology, metabolism)
- Gram-Negative Bacterial Infections
(immunology)
- Humans
- Immunity, Innate
- Lipopolysaccharide Receptors
(immunology, metabolism)
- Lipopolysaccharides
(immunology, metabolism)
- Lymphocyte Antigen 96
(immunology, metabolism)
- Membrane Proteins
(immunology, metabolism)
- Signal Transduction
- Toll-Like Receptors
(immunology, metabolism)
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