Mice deficient in TLR4 have an increased susceptibility to infection with Gram-negative bacteria (O'Brien et al., 1980; Cross et al., 1989), but excessive activation of NFκB can lead to septic shock (Liu and Malik, 2006), and inappropriate TLR4 activation, for example, by nickel ligands (Schmidt et al., 2010) or house-dust-mite allergen Derp2, which is structurally and functionally similar to MD-2 (Trompette et al., 2009), can lead to allergy. This evidence concerns the gene TLR4 and allergic disease.