Evidence for an accessory protein function for toll-like receptor 1 in anti-bacterial responses

Members of the Toll-like receptor (TLR) family are components of the mammal ian anti-microbial response, signaling with a domain closely related to tha t of IL-L receptors, In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as d emonstrated using a novel mAb. Monocytes also express TLR2, TLR1 transfecti on of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient t o confer responsiveness to several microbial extracts. However, cotransfect ion of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to solubl e factors released from Neisseria meningitidis relative to the response wit h either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS, The N, meningitidis factors recognized by TLR1 /TLR2 were not released by N, meningitidis mutant in the LpxA gene. Althoug h LpxA is required for LPS biosynthesis, because cooperation between TLR1 a nd TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS, The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TL R1 and TLR2, for certain agonists, These data further suggest that mammalia n responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-me diated responses.