Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide.

ABSTRACT: Toll-like receptor 4 (TLR4) induces inflammation in response to both pathogen- and host-derived molecules. Lipopolysaccharide (LPS) recognition by TLR4 has been shown to occur across the amniotes, but endogenous signaling through TLR4 has not been validated outside of placental mammals. To determine whether endogenous danger signaling is also shared across amniotes, we studied the evolution of TLR4-activation by the calgranulin proteins (S100A8, S100A9, and S100A12), a clade of host molecules that potently activate TLR4 in placental mammals. We performed phylogenetic and syntenic analysis and found MRP-126-a gene in birds and reptiles-is likely orthologous to the mammalian calgranulins. We then used an ex vivo TLR4 activation assay to establish that calgranulin pro-inflammatory acti

SUBMITTER: Loes AN 

PROVIDER: S-EPMC5826337 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature