In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component
chitin. We observed that repeated aspirations of the high-
chitin-expressing isolate Af5517 induced increased airway
eosinophilia in the lungs of recipient mice compared to the level of
eosinophilia induced by isolate Af293. CD4(+) T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased
gamma interferon secretion and increased
interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated
chemokines CCL11 (eotaxin-1) and CCL22 (
macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of
chitin exposure during germination and was decreased by constitutive lung
chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and
infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of
chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus
infection.