Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caus ed by an opportunistic fungal pathogen, Aspergillus fumigatus (Afu), Lung s urfactant proteins SP-A and SP-D can interact with the glycosylated antigen s and allergens of Afu, inhibit specific IgE binding to these allergens, an d block histamine release from sensitized basophils. We have now examined t he therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hype rsensitivity induced by Afu antigens and allergens, which resembles human A BPA immunologically. The ABPA mice exhibited high levels of Afu-specific Ig G and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eo sinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA m ice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indic ating a marked shift from Th2 to Th1 response. These results clearly implic ate pulmonary SP-A and SP-D in the modulation of allergic reactions.