Induction of direct antimicrobial activity through mammalian toll-like receptors.
The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.
Thoma-Uszynski
S
S
Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Stenger
S
S
Takeuchi
O
O
Ochoa
M T
MT
Engele
M
M
Sieling
P A
PA
Barnes
P F
PF
Rollinghoff
M
M
Bolcskei
P L
PL
Wagner
M
M
Akira
S
S
Norgard
M V
MV
Belisle
J T
JT
Godowski
P J
PJ
Bloom
B R
BR
Modlin
R L
RL
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D029721:Drosophila Proteins; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008024:Ligands; D008074:Lipoproteins / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008024:Ligands; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse