A Single Step in vitro Bioassay Mimicking TLR4-LPS Pathway and the Role of MD2 and CD14 Coreceptors.

ABSTRACT: Acute systemic Gram-negative bacterial infections are accompanied by release of lipopolysaccharide (LPS) endotoxins into the bloodstream and an innate immune host response via the well-known toll like receptor 4 (TLR4) pathway. In this, LPS associates non-covalently with TLR4 to form an activated heterodimer (LPS/MD2/TLR4)₂ complex in vivo, assisted by a coreceptor CD14. This complexation process has been illustrated ex vivo using indirect methods such as cytokine, interleukin, TNF-α measurements and by direct demonstration of sequential binding events on a surface using advanced optics. We are the first ones to carry out homogeneous self-assembly of LPS-rTLR4-MD2 conjugates in vitro in a single step, and further demonstrate the role of CD14 as a catalyst du

SUBMITTER: Jagtap P 

PROVIDER: S-EPMC6992608 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature