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TB, or not TB: that is the question – does TLR signaling hold the answer?
Terence M. Doherty, Moshe Arditi
Terence M. Doherty, Moshe Arditi
Published December 15, 2004
Citation Information: J Clin Invest. 2004;114(12):1699-1703. https://doi.org/10.1172/JCI23867.
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Commentary

TB, or not TB: that is the question – does TLR signaling hold the answer?

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Abstract

Innate immunity critically depends on signaling by Toll-like receptors (TLRs) that rely heavily on an intracellular adapter protein called myeloid differentiation factor 88 (MyD88). Adaptive immune defenses are generally thought to be orchestrated by innate immune responses and so should require intact TLR-MyD88 signaling pathways. But a surprising new study in MyD88-null mice infected with Mycobacterium tuberculosis challenges this view and instead suggests that MyD88 may not be absolutely required for a normal adaptive immune response.

Authors

Terence M. Doherty, Moshe Arditi

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Figure 1

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MyD88-dependent and MyD88-independent TLR signaling pathways. Most TLRs ...
MyD88-dependent and MyD88-independent TLR signaling pathways. Most TLRs require MyD88; however, TLR4 can transmit signals by utilizing the alternative adapters, TRAM and TRIF. Like MyD88, this sub-pathway can activate NF-κB, but can regulate transcription of target genes in a manner that may be distinct from that elicited by the classical MyD88-dependent route. HSP65, heat shock protein 65; LAM, lipoarabinomannan; LM, lipomannan; PIMs, phosphatidyl-myoinositol mannosidases; STF, soluble tuberculosis factor; TIRAP, TIR domain–containing adapter protein.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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