immunology of infectious and parasitic diseases - XXXVII Congress ...

The Role of Eosinophils in Aspergillus fumigatus Lung Infection
FREDERICO MARIANETTI SORIANI 1 ; REMO CASTRO RUSSO 2 ; CAMILA
RODRIGUES CHAVES NOGUEIRA 4 ; LIRLÂNDIA PIRES DE SOUSA 4 ;
MILENE ALVARENGA RACHID 3 ; MAURO MARTINS TEIXEIRA 1 : 1 Bioquímica
e Imunologia, 2 Fisiologia, 3 Patologia, ICB; 4 Farmácia, Universidade Federal de
Minas Gerais, Belo Horizonte, Brasil.
Introduction: Eosinophils are important in the pathophysiology of allergic
diseases and in host immunity. Although microorganisms directly activate
inflammatory cells, the mechanisms that trigger eosinophils activation and its
functions in immune responses are unknown. Fungi are ubiquitous and may
contribute to the development and exacerbation of pulmonary diseases. In this
sense, the aim of this study was to unravel the role of eosinophils during
Aspergillus fumigatus lung infection. Methods and Results: Wild type (BALB/c)
and ΔdblGATA mice were infected intranasally with 10 8 spores of an A.
fumigatus wild type strain. Lungs and BALFs were collected from animals after
1 and 3 days post infection and used for the analysis. Results show that
ΔdblGATA mice had increased survival (40% versus 100% in WT mice). PMN
influx in the lungs 1dpi was greater in ΔdblGATA mice (1,641±76.3), compared
to wild type (392.7±139.1), while macrophage influx to the airways was reduced
in ΔdblGATA mice after 3 days of infection (10.6±2.1x10 6 cells/BALF) compared
to wild type (21.1±2.7x10 6 cells/BALF). However, besides cell influx there was
less protein leakage 3 dpi in ΔdblGATA mice (2,224±172 versus 3,195±275).
Levels of eosinophils were very high in lungs and airways of WT mice after A.
fumigatus infection but not detectable in ΔdblGATA mice. Airway levels of
CXCL1, TNF-α, CCL11, CCL2 and IL-1β were reduced in ΔdblGATA mice
(638.5±205; 865±93; 163±13; 265±8.6 and 19.8±3.5, respectively) compared to
wild type (1,771±79; 1,858±197; 216±26; 378±8.3 and 79.4±17.6, respectively).
Interestingly, histopathological analysis did not show any differences between
animals. Fungal burden was higher in ΔdblGATA than WT mice after
1(11.5±0.7x10 5 versus 8.6±0.5x10 5 UFC) and 3 dpi (0.46±0.15x10 5 versus
0.15±0.05x10 5 UFC). Conclusion: In conclusion, the absence of eosinophils
leads to decreased production of key cytokines and increased fungal burden
after infection with A. fumigatus. However, this is associated with enhanced
neutrophil influx and survival, suggesting that eosinophils are crucial in setting
the appropriate tone of the immune response to infection by A. fumigatus.
Financial Support: CNPq, Capes, FAPEMIG.