Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products

Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here, we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia. and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4 independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response and potentially impact the development of allergic airway disease to environmental fungal antigens.