The study by Underhill et al. (1999) investigates the role of toll-like receptors (TLRs) in macrophage responses to *Mycobacterium tuberculosis*. They demonstrate that TLR2 is essential for the induction of tumor necrosis factor α (TNF-α) production in macrophages upon exposure to *M. tuberculosis*. The authors show that expression of a dominant negative form of MyD88, a signaling component required for TLR signaling, blocks TNF-α production. They identify TLR2 as the specific TLR required for this induction by demonstrating that expression of an inhibitory TLR2 mutant (TLR2-P681H) blocks TNF-α production. Further, they show that TLR2-dependent signaling mediates responses to various fractions of the mycobacterial cell wall, including liparabinomannan, mycolylarabinogalactan-peptidoglycan complex, and total lipids. These findings suggest that TLR2 is crucial for the induction of a protective immune response to *M. tuberculosis*. The study also highlights the distinct signaling mechanisms of TLR2 compared to TLR4, which is involved in LPS-induced signaling.The study by Underhill et al. (1999) investigates the role of toll-like receptors (TLRs) in macrophage responses to *Mycobacterium tuberculosis*. They demonstrate that TLR2 is essential for the induction of tumor necrosis factor α (TNF-α) production in macrophages upon exposure to *M. tuberculosis*. The authors show that expression of a dominant negative form of MyD88, a signaling component required for TLR signaling, blocks TNF-α production. They identify TLR2 as the specific TLR required for this induction by demonstrating that expression of an inhibitory TLR2 mutant (TLR2-P681H) blocks TNF-α production. Further, they show that TLR2-dependent signaling mediates responses to various fractions of the mycobacterial cell wall, including liparabinomannan, mycolylarabinogalactan-peptidoglycan complex, and total lipids. These findings suggest that TLR2 is crucial for the induction of a protective immune response to *M. tuberculosis*. The study also highlights the distinct signaling mechanisms of TLR2 compared to TLR4, which is involved in LPS-induced signaling.