Initial responses to endotoxins and Gram-negative bacteria
| Autor: | Didier Heumann, Thierry Roger |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Gram-negative bacteria Lipopolysaccharide CD14 Clinical Biochemistry Lipopolysaccharide Receptors Receptors Cell Surface Biology Biochemistry Microbiology chemistry.chemical_compound Immune system Gram-Negative Bacteria Animals Drosophila Proteins Humans Toll-like receptor Membrane Glycoproteins Innate immune system Macrophages Toll-Like Receptors Biochemistry (medical) General Medicine Acquired immune system biology.organism_classification Immunity Innate Endotoxins Toll-Like Receptor 4 chemistry Immunology TLR4 Carrier Proteins Gram-Negative Bacterial Infections Acute-Phase Proteins |
| Zdroj: | Clinica Chimica Acta. 323:59-72 |
| ISSN: | 0009-8981 |
| Popis: | The innate immune system initiates host defence against invasive microbial pathogens using specific recognition mechanisms. Here we review the current concepts and the molecular basis of innate immune responses to bacterial infections, focusing our attention on the actors involved in the response to Gram-negative bacteria. Lipopolysaccharide (LPS) is the major virulence factor of Gram-negative bacteria. During the past decade, enormous progress has been obtained in the elucidation of LPS recognition and signalling in mammalian phagocytes. According to the current model, recognition of LPS is initialized by the cooperative interplay between the LPS-binding protein (LBP), the membrane-bound or soluble forms of CD14 and the recently identified Toll-like receptor 4 (TLR4)-MD-2 complex. Recognition of LPS leads to the rapid activation of an intracellular signalling pathway, highly homologous to the signalling pathway of interleukin-1, which results in the release of pro-inflammatory mediators. In vivo models in which animals are challenged with LPS or Gram-negative bacteria have highlighted opposite roles for LBP, CD14 and TLRs. Regarding LPS challenge, there is a large body of evidence in favour of a detrimental role played by LBP, CD14 and TLRs. These molecules sensitize the host to a LPS-induced uncontrolled acute inflammatory response that results in animal death. However, when the host is in the presence of virulent Gram-negative bacteria, the invading pathogens must be held in check by the innate immune system until a specific immune response is mounted. Under these conditions, LBP, CD14 and TLRs are required to trigger a pro-inflammatory response which is crucial for keeping infection under control. Therefore, caution should be the rule about the development of therapeutic approaches aimed at blocking the pro-inflammatory response during Gram-negative infections. |
| Databáze: | OpenAIRE |
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