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Different Toll‐like receptor agonists induce distinct macrophage responses
Author(s) -
Jones Bryan W.,
Means Terry K.,
Heldwein Kurt A.,
Keen Marc A.,
Hill Preston J.,
Belisle John T.,
Fenton Matthew J.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.6.1036
Subject(s) - biology , tlr2 , toll like receptor , tumor necrosis factor alpha , lipopolysaccharide , microbiology and biotechnology , lipoarabinomannan , agonist , kinase , receptor , secretion , signal transduction , tlr4 , biochemistry , mycobacterium tuberculosis , immunology , innate immune system , medicine , tuberculosis , pathology
We previously reported that gram‐negative bacterial lipopolysaccharide (LPS) activates cells via Toll‐like receptor (TLR) 4, whereas the mycobacterial cell wall glycolipid lipoarabinomannan (LAM) activates cells via TLR2. We also identified a secreted TLR2 agonist activity in short‐term culture filtrates of Mycobacterium tuberculosis bacilli, termed soluble tuberculosis factor (STF). Here we show that STF contains mannosylated phosphatidylinositol (PIM) and that purified PIM possesses TLR2 agonist activity. Stimulation of RAW 264.7 macrophages by LPS, LAM, STF, and PIM rapidly activated nuclear factor (NF)‐κB, activator protein‐1 (AP‐1), and mitogen‐activated protein (MAP) kinases. These TLR agonists induced similar levels of NF‐κB and AP‐1 DNA‐binding activity, as well as trans ‐activation function. Unexpectedly, these TLR agonists induced tumor necrosis factor α secretion, whereas only LPS was capable of inducing interleukin‐1β and nitric oxide secretion. Thus, different TLR proteins are still capable of activating distinct cellular responses, in spite of their shared capacities to activate NF‐κB, AP‐1, and MAP kinases.