Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases.

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State: Public
Version: Final published version
Serval ID
serval:BIB_F8A91FB09BA8
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
Title
Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases.
Journal
Frontiers in Immunology
Author(s)
Savva A., Roger T.
ISSN
1664-3224 (Print)
ISSN-L
1664-3224
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
4
Pages
387
Language
english
Notes
Publication types: REVIEW Publication Status: epublish
Abstract
Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.
Pubmed
Web of science
Open Access
Yes
Create date
09/12/2013 17:15
Last modification date
20/08/2019 17:24
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