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Interleukin-4 Causes Susceptibility to Invasive Pulmonary Aspergillosis through Suppression of Protective Type I Responses

Cenci, Elio ; Mencacci, Antonella ; Del Sero, Giuseppe ; Bacci, Angela ; Montagnoli, Claudia ; Fè d'Ostiani, Cristiana ; Mosci, Paolo ; Bachmann, Martin ; Bistoni, Francesco ; Kopf, Manfred ; Romani, Luigina

In: Journal of Infectious Diseases, 1999, vol. 180, no. 6, p. 1957-1968

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    Titel
    • Interleukin-4 Causes Susceptibility to Invasive Pulmonary Aspergillosis through Suppression of Protective Type I Responses
    Autor
    • Cenci, Elio. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Mencacci, Antonella. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Del Sero, Giuseppe. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Bacci, Angela. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Montagnoli, Claudia. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Fè d'Ostiani, Cristiana. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Mosci, Paolo. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Bachmann, Martin. 2Basel Institute for Immunology, Basel, Switzerland
    • Bistoni, Francesco. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Kopf, Manfred. 2Basel Institute for Immunology, Basel, Switzerland
    • Romani, Luigina. 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Journal of Infectious Diseases, 1999, vol. 180, no. 6, p. 1957-1968. The University of Chicago Press
    Andere elektronische Ausgabe
    Klassifikation
    • Gesundheit
    OAI-PMH-ID
    • oai:doc.rero.ch:293208
    Summary
    Aspergillus fumigatus, an opportunistic fungal pathogen, causes multiple allergic and non-allergic airway diseases. Invasive pulmonary aspergillosis (IPA) is a nonallergic, life-threatening disease of immunocompromised patients. In a murine model of IPA, interleukin (IL)—4-deficient (IL-4−/−) BALB/c mice were used to examine the role of IL-4 in lung pathology and immune responses. IL-4−/− mice were more resistant than wild-type mice to infection caused by multiple intranasal injections of viable A. fumigatus conidia. Resistance was associated with decreased lung inflammatory pathology, impaired T helper (Th)—2 responses (including lung eosinophilia), and an IL-12—dependent Th1 response. In contrast, development of host-detrimental antifungal Th2 cells occurred in IL-12−/− and interferon-γ−/− mice and in IL-4−/− mice when subjected to IL-12 neutralization. These results demonstrate that IL-4 renders mice susceptible to infection with A. fumigatus by inhibition of protective Th1 responses. IL-4 appears to have a distinct role in the pathogenesis of allergic and nonallergic lung diseases caused by the fungus