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*
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy; and
Allergy-Immunology Division, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee, WI 53295
Aspergillus fumigatus, an opportunistic fungal
pathogen, is responsible for multiple airway diseases of an allergic
and a nonallergic nature. In a murine model of invasive pulmonary
aspergillosis, resistance is associated with a decreased lung
inflammatory pathology and the occurrence of an IL-12-dependent
Th1-type reactivity that are both impaired by IL-4. In the present
study we assess the ability of Aspergillus crude culture
filtrate Ags and the recombinant allergen Asp f 2 to induce protective
antifungal responses in mice with invasive pulmonary aspergillosis.
Similar to what occurred upon nasal exposure to viable A.
fumigatus conidia, treatment of immunocompetent mice with
Aspergillus crude culture filtrate Ags resulted in the
development of local and peripheral protective Th1 memory responses,
mediated by Ag-specific CD4+ T cells producing IFN-
and
IL-2 capable of conferring protection upon adoptive transfer to naive
recipients. Protective Th1 responses could not be observed in mice
deficient of IFN- or IL-12 and did not occur in response to Asp f 2,
which, on the contrary, elicited high level production of inhibitory
IL-4. The results show that Ags of Aspergillus exist
with the ability to induce both Th1- and Th2-type reactivity during
infection, a finding that suggests a possible mechanism through which
potentially protective immune responses are inhibited in mice with the
infection. However, the occurrence of Th1-mediated resistance upon
vaccination with Aspergillus crude culture filtrate Ags,
suggests the existence of fungal Ags useful as a candidate vaccine
against invasive pulmonary aspergillosis.
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