Histamine receptor 2 is a key influence in immune responses to intestinal histamine-secreting microbes

Histamine exerts its immunoregulatory effects via the activation of 4 different histamine receptors (named H1R to H4R).4 Activation of histamine receptor 2 (H2R) is associated with potent immunoregulatory effects, and the anti-inflammatory effects of a histamine-secreting L rhamnosus strain were lost in H2R-deficient animals, suggesting that histamine derived from the microbiota could be immunoregulatory.5 To extend this observation and determine whether this phenomenon is a common feature of histamine-secreting microbes, we performed in vitro and murine studies with another Lactobacillus that is well recognized for its ability to secrete high levels of histamine, L saerimneri strain 30a (ATCC 33222).6 In vitro, the strain performed as expected. In vitro studies have demonstrated that TLR responses to microbial ligands are significantly influenced by histamine signaling through H2R.5,8 In this report, we demonstrate that the H2R is required for IL-6 and IL-17 mucosal responses, suggesting that H2R is a critical immunoregulatory receptor that significantly influences the in vivo immune response to histamine-secreting microbes within the intestine.