Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses.

Journal article

Aspergillus fumigatus, an opportunistic fungal pathogen, causes multiple allergic and nonallergic 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-gamma-/- 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.

Authors: Cenci, E; Mencacci, A; Del Sero, G; Bacci, A; Montagnoli, C

• Publication status: Published
• Journal: Journal of infectious diseases
• Volume: 180
• Issue: 6
• Pages: 1957-1968
• Publication date: 1999-12-01
• DOI: 10.1086/315142
• EISSN: 1537-6613
• ISSN: 0022-1899
• Language: English
• Keywords: Bronchoalveolar Lavage Fluid; Female; Aspergillosis; Lung Diseases, Fungal; Mice, Inbred BALB C; Immune Tolerance; Lymphocytes; Flow Cytometry; Lung; Interleukin-4; Mice; Lymphocyte Activation; Th1 Cells; Disease Models, Animal; Humans; Aspergillus fumigatus; Mice, Inbred DBA; Th2 Cells; Mice, Knockout; Animals