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* The Pulmonary Center, Boston University School of Medicine, Boston Massachusetts, and
Mycobacteria Research Laboratories, Department of Microbiology, Colorado State University, Ft. Collins, Colorado
Correspondence: Dr. Matthew J. Fenton, Pulmonary Center R-220, Boston University School of Medicine, 80 East Concord St., Boston MA 02118-2394. E-mail: mfenton{at}bu.edu
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)-
B, activator protein-1 (AP-1), and mitogen-activated protein
(MAP) kinases. These TLR agonists induced similar levels of NF-
B and
AP-1 DNA-binding activity, as well as trans-activation
function. Unexpectedly, these TLR agonists induced tumor necrosis
factor
secretion, whereas only LPS was capable of inducing
interleukin-1ß 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-
B, AP-1, and MAP
kinases.
Key Words: signal transduction tuberculosis innate immunity
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