Toll-like receptor 2 (TLR2) and TLR4 are pattern-recognition molecules with an important role in the early innate immune response to microbial challenge, but their presence on mast cells remains unexplained. In 15 May Journal of Clinical Investigation, Volaluck Supajatura and colleagues from Juntendo University School of Medicine, Tokyo, Japan, show that direct activation of mast cells via TLR2 or TLR4 by respective microligands contributes to innate and allergic immune responses (J Clin Invest 2002, 109:1351-1359).

Supajatura et al. used bone marrow–derived mast cells from TLR2 or TLR4 gene-targeted mice. They found that TLR4, which binds the gram-negative product lipopolysaccharide, and TLR2, which binds peptidoglycan (PGN) from gram-positive organisms (e.g. Staphylococcus aureus) induce distinct mast cell responses. In addition, they showed that TLR4-mediated activation of peritoneal mast cells is crucial for host protection from Gram-negative bacterial infection, whereas TLR2-mediated activation of skin mast cells causes acute and late reactions by PGN application and may exacerbate the inflammatory lesions of atopic dermatitis, in which S aureus infection is common.

"Finding the microbial ligands and relevant receptors on mast cells, as well as signaling pathways that can activate mast cells, will elucidate the complexity of innate immunity and the roles of mast cells in conditions other than allergy" conclude the authors.