This information is current as Lung Infiltration Home Environments Induces Eosinophilic Fungal Chitin from Asthma-Associated and

Development of asthma and allergic inflammation involves innate immunity, but the environmental contributions remain incompletely defined. Analysis of dust collected from the homes of asthmatic individuals revealed that the polysaccharide chitin is environmentally widespread and associated with b-glucans, possibly from ubiquitous fungi. Cell wall preparations of Aspergillus isolated from house dust induced robust recruitment of eosinophils into mouse lung, an effect that was attenuated by enzymatic degradation of cell wall chitin and b-glucans. Mice expressing constitutively active acidic mammalian chitinase in the lungs demonstrated a significant reduction in eosinophil infiltration after fungal challenge. Conversely, chitinase inhibition prolonged the duration of tissue eosinophilia. Thus, fungal chitin derived from home environments associated with asthma induces eosinophilic allergic inflammation in the lung, and mammalian chitinases, including acidic mammalian chitinase, limit this process. T he rise in asthma and allergic disorders appears to involve intersecting genetic and environmental factors, such that genetically susceptible individuals develop disease that can be triggered or exacerbated by one or more of the myriad insults encountered by the airway mucosa (1). This external environment comprises a diverse mix of potentially allergenic materials ; however, certain common components have emerged as candidates underlying the persistent immune activation associated with these chronic conditions. Among them, fungi and fungal-derived bioactive agents, prominent as ubiquitous constituents of airborne particulate matter and inhaled house dust, have been linked to severe asthma and allergic conditions, and pose an additional systemic threat to immunocompromised individuals (2, 3). Inhaled conidia from Aspergillus species and other fungi are normally immunologically silent due to the presence of a surface hydrophobin layer that prevents recognition (4), together with rapid phagocyte-oxidase–mediated killing by alveolar macrophages (5). Impairment of this process, however, can result in conidial germination, leading to the recruitment of inflammatory cells such as eosinophils and neutrophils, which are able to inhibit hyphal growth (3, 6). Interestingly, immune triggering only occurs with concomitant conidial swelling and hyphal growth, a process linked to exposure and recognition of fungal cell wall b-glucan polymers (7–9). In addition to b-glucans, the fungal cell wall contains chitin, a polysaccharide consisting of linear b-1,4-N-acetylglucosamine, which is intimately interconnected with b-glucans, galactomannans, and mannoproteins to form the structural foundation of the hyphal cell wall (10). Recently, chitin has been identified as a recognition element capable of initiating innate immune responses associated with allergy and asthma (11), but whether chitin induces immunologic activity as a constituent of natural …