Gluten in wheat, barley and rye can induce pathology in the small intestine, such as celiac disease, due to the immunogenicity of several nondegraded gluten peptides that trigger activation of T cells in susceptible people who express HLA-DQ2 and HLA-DQ8. In the Journal of Experimental Medicine, Junker et al. show that α-amylase–trypsin inhibitors (ATIs), which have a role in pest resistance in cereals, are strong inducers of innate immune responses in mice and humans. ATIs engage the TLR4-MD2-CD14 complex and elicit inflammatory cytokines such as interleukin 8 (IL-8), IL-12, TNF, CCL2 and CCL5 in DCs, monocytes and macrophages and induce intestinal inflammation in mice deficient in recombination-activating gene 1. ATIs induce a similar degree of activation in DCs from healthy controls and patients with celiac disease, which indicates that this activating interaction might be controlled in healthy people.

J. Exp. Med. 209, 2395–2408 (2012)