Initial responses to endotoxins and Gram-negative bacteria
Details
Serval ID
serval:BIB_1BAA41567071
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Initial responses to endotoxins and Gram-negative bacteria
Journal
Clinica Chimica Acta
ISSN
0009-8981 (Print)
Publication state
Published
Issued date
09/2002
Volume
323
Number
1-2
Pages
59-72
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Sep
Research Support, Non-U.S. Gov't
Review --- Old month value: Sep
Abstract
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.
Keywords
*Acute-Phase Proteins
Animals
Antigens, CD14/metabolism
Carrier Proteins/metabolism
*Drosophila Proteins
Endotoxins/*immunology
Gram-Negative Bacteria/*immunology
Gram-Negative Bacterial Infections/*immunology
Humans
Immunity, Natural
Lipopolysaccharides/immunology
Macrophages/immunology
Membrane Glycoproteins/metabolism
Receptors, Cell Surface/metabolism
Toll-Like Receptor 4
Toll-Like Receptors
Pubmed
Web of science
Create date
25/01/2008 14:35
Last modification date
20/08/2019 13:52