BACKGROUND: The initial immune response to house dust mite (HDM) is orchestrated by an interplay between epithelial cells (ECs) and dendritic cells (DCs). Innate cytokines released by HDM-exposed ECs activate airway DCs and effector inflammatory cells, which together induce a HDM-specific Th2 cell response. Here, we investigate the respective roles of DCs and IL-33 in sensitization to HDM. METHOD: Balb/c mice were exposed via the airways to different HDM extracts, differing in at least endotoxin levels [Lotox (LT) and HiTox (HT)]. Alternatively, HDM-pulsed DCs in the presence or absence of additional LT-HDM, or administration of LT-HDM plus recombinant IL-33, were intratracheally (i.t.) administered to induce allergic airway inflammation. Eosinophil recruitment, cytokine production, serum immunoglobulins, and airway histology were analyzed. RESULTS: Direct exposure of airways with HT-HDM induced an eosinophilic airway inflammation, Th2 cytokine production, and an increase in total IgE and HDM IgG1, while LT-HDM was not able to do so. In contrast, i.t. instillation of LT-HDM-pulsed DCs induced a similar airway inflammation, mucus production, and cytokine production, but IgE or HDM IgG1 was not induced. Administration of HDM-pulsed DCs together with LT-HDM, to supply B cells with unprocessed antigen, was not sufficient to induce antibody production. Simultaneous administration of recombinant IL-33 with LT-HDM induced an antibody response, besides a cellular immune response. CONCLUSION: These results demonstrate that HDM-pulsed DCs were able to drive a Th2 response but that IL-33 was needed to induce a humoral immune response to a single inhalational challenge to HDM.
BACKGROUND: The initial immune response to house dust mite (HDM) is orchestrated by an interplay between epithelial cells (ECs) and dendritic cells (DCs). Innate cytokines released by HDM-exposed ECs activate airway DCs and effector inflammatory cells, which together induce a HDM-specific Th2 cell response. Here, we investigate the respective roles of DCs and IL-33 in sensitization to HDM. METHOD: Balb/c mice were exposed via the airways to different HDM extracts, differing in at least endotoxin levels [Lotox (LT) and HiTox (HT)]. Alternatively, HDM-pulsed DCs in the presence or absence of additional LT-HDM, or administration of LT-HDM plus recombinant IL-33, were intratracheally (i.t.) administered to induce allergic airway inflammation. Eosinophil recruitment, cytokine production, serum immunoglobulins, and airway histology were analyzed. RESULTS: Direct exposure of airways with HT-HDM induced an eosinophilic airway inflammation, Th2 cytokine production, and an increase in total IgE and HDM IgG1, while LT-HDM was not able to do so. In contrast, i.t. instillation of LT-HDM-pulsed DCs induced a similar airway inflammation, mucus production, and cytokine production, but IgE or HDM IgG1 was not induced. Administration of HDM-pulsed DCs together with LT-HDM, to supply B cells with unprocessed antigen, was not sufficient to induce antibody production. Simultaneous administration of recombinant IL-33 with LT-HDM induced an antibody response, besides a cellular immune response. CONCLUSION: These results demonstrate that HDM-pulsed DCs were able to drive a Th2 response but that IL-33 was needed to induce a humoral immune response to a single inhalational challenge to HDM.