New insights into the aryl hydrocarbon receptor as a modulator of host responses to infection.

The host response to infection is known to be influenced by many factors, including genetics, nutritional status, age, as well as drug and chemical exposures. Recent advances reveal that the aryl hydrocarbon receptor (AhR) modulates aspects of the innate and adaptive immune response to viral, bacterial, and parasitic organisms. Although many of these observations were made using the high affinity but poorly metabolized AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), not all of the effects are detrimental to the host. Sometimes AhR activation, even with TCDD, was beneficial and improved host resistance and survival. A similar dichotomy is observed in infected AhR-deficient mice, wherein absence of functional AhR sometimes, but not always, alters host resistance. When examined in their totality, current data indicate that AhR controls multiple regulatory pathways that converge with infection-associated signals and depending on the context (e.g., type of pathogen, site of infection), lead to distinct outcomes. This creates numerous exciting opportunities to harness the immunomodulatory action of AhR to transform host responses to infection. Moreover, since many of the mechanisms cued in response to infectious agents are pivotal in the context of other diseases, there is much to be learned about AhR's cellular targets and molecular mechanisms of action.