Cutting edge: Cells that carry a null allele for toll-like receptor 2 are capable of responding to endotoxin

Toll-like receptor (TLR)2 and TLR4 have been implicated in the responses of cells to LPS (endotoxin). CD14-transfected Chinese hamster ovary (CHO)-K1 fibroblasts (CHO/CD14) are exquisitely sensitive to endotoxin, Sequence ana lysis of CHO-TLR2, compared with human and mouse TLR2, revealed a single ba se pair deletion. This frameshift mutation resulted in an alternative stop codon, encoding a protein devoid of transmembrane and intracellular domains . CHO-TLR2 cDNA failed to enable LPS signaling upon transient transfection into human epithelial kidney 293 cells. Site-directed mutagenesis of CHO-TL R2 enabled expression of a presumed full-length hamster TLR2 that conferred LPS responsiveness in human epithelial kidney 293 cells, Genomic TLR2 DNA from primary hamster macrophages also contained the frameshift mutation fou nd in CHO fibroblasts, Nevertheless, hamster peritoneal macrophages were fo und to respond normally to LPS, as evidenced by the induction of cytokines, These results imply that expression of TLR2 is sufficient but not essentia l for mammalian responses to endotoxin.