Monocyte antimicrobial activities are differentially triggered by TLR2/1 and TLR2/6 activation (134.91)

Abstract

Abstract Human innate immune responses against microbial pathogens are mediated in part by Toll-like receptors (TLR). We have previously demonstrated that the 19kD lipoprotein, a TLR2/1 ligand, induces a vitamin D-dependent killing of Mycobacterium tuberculosis in infected monocytes; however the ability of the other TLR family members to induce this pathway is unclear. Given that TLRs instruct the innate immune response to different types of pathogens, we hypothesize the TLR family members will differentially regulate antimicrobial activity. While 19kD is able to induce killing in infected macrophages, macrophage activating lipopeptide 2 (MALP-2), a TLR2/6 ligand, did not. We investigated the differences in gene expression profiles between 19kD and MALP-2 treated monocytes, which yielded differentially expressed gene programs. Interleukin-10 family members were found to be upregulated in 19kD treated monocytes as compared to monocytes treated with MALP-2. In MALP-2 treated monocytes, leukocyte immunoglobulin-like receptors (LIR) were found to be upregulated. Investigating these differentially regulated genes can yield information that could results therapeutic targets against intracellular pathogens.