Aspergillus-induced eosinophil recruitment to murine lung is dependent on cell wall polysaccharides (80.9)

Abstract Development of allergic inflammation in response to fungal organisms involves innate immunity, but initial molecular recognition events remain unclear. We sought to identify elements of Aspergillus essential to initiating allergic inflammation using IL-4-GFP reporter (4get) mice. Intranasal administration of an Aspergillus preparation resulted in robust recruitment of innate immune cells to the lungs of 4get mice, independent of protease activity, implicating cell wall components. The major cell wall polysaccharides of Aspergillus include chitin, along with linear and branched β-glucan polymers, both of which can initiate innate immune responses in mammals. Enzymatic degradation of either chitin or β-glucans led to significant reductions in the magnitude of eosinophil recruitment to the lungs of 4get mice after intranasal Aspergillus administration, an effect that was enhanced additively by degradation of both polysaccharides. The specific contribution of chitin was examined using 4get-SPAM mice, which express elevated levels of acidic mammalian chitinase in the lungs and thus possess an enhanced ability to degrade chitin in vivo. After Aspergillus challenge, lung eosinophils numbers in 4get-SPAM mice were significantly diminished compared to 4get-WT littermates, in both acute and extended dosing regimens, while eosinophils remained at WT levels when challenged similarly with ovalbumin. These data reveal a previously unidentified link between specific polysaccharide recognition and eosinophil recruitment during Aspergillus-induced allergic lung inflammation.