Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses.
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.
Cenci
E
E
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Mencacci
A
A
Del Sero
G
G
Bacci
A
A
Montagnoli
C
C
d'Ostiani
C F
CF
Mosci
P
P
Bachmann
M
M
Bistoni
F
F
Kopf
M
M
Romani
L
L
D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015847:Interleukin-4