House dust extracts have both TH2 adjuvant and tolerogenic activities

BackgroundAlthough mechanisms remain a subject of controversy, there is general agreement that living environments influence allergic risk during the first years of life. We reasoned that sterile house dust extracts (HDEs) would have immunologic activities reflective of their environments of origin and therefore would be useful surrogates for investigations of how ambient exposures influence immune homeostasis.ObjectiveThese experiments determined how airway HDE exposures influence adaptive responses to a coadministered antigen and subsequent airway hypersensitivity responses to antigen challenge.MethodsMice received intranasal ovalbumin (OVA) vaccinations on a weekly basis. Select groups of mice also received intranasal HDE weekly with OVA; daily at one seventh the weekly dose, beginning 7 days before the first OVA sensitization; or both.ResultsWeekly intranasal vaccinations with OVA and HDE primed mice for the development of TH2-biased immune and airway hypersensitivity responses. In contrast, daily low-dose intranasal HDE exposures protected against the immunologic and pathologic outcomes associated with weekly intranasal OVA/HDE vaccinations. The TH2 adjuvant activities of HDEs were found to be dependant on MyD88, a molecule critical for signaling through a majority of Toll-like receptors. Moreover, the tolerogenic activity associated with daily intranasal HDE exposures could be replicated with LPS.ConclusionThese investigations demonstrate that in addition to allergens, living environments contain immunomodulatory materials with both TH2 adjuvant and tolerogenic activities.Clinical implicationsAs the contents of HDEs are ubiquitous, these experiments might recapitulate and help explain clinically relevant immunologic events involved in the maintenance of aeroallergen tolerance and the dysregulated responses that lead to allergic respiratory diseases.