DIFFERENTIAL CELLULAR IMMUNE RESPONSE IN BAL AFTER INHALATION OF PIGEON SERUM AND ASPERGILLUS EXTRACT IN ACUTE AND CHRONIC MURINE MODELS OF HYPERSENSITIVITY PNEUMONITIS

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of, mainly, avian and fungal antigens. However, the immunological mechanisms involved are not yet well understood. The objective of the study was to compare the cellular immune response after exposure to pigeon serum and Aspergillus sp. extract in acute and chronic murine models of hypersensitivity pneumonitis (HP). The animal models were conducted using C57BL/6J strain mice. The HP groups were sensitized with two injections (48 hours apart) of 100 µL of pigeon serum (200 µg/ml) for the avian-origin HP group (HPA) and Aspergillus extract (200 µg/ml) for the fungal-origin HP group (HPF). The control group was sensitized with saline serum. Antigen exposure was performed via intranasal instillations of 40 µL on three consecutive days per week for three weeks in acute model and sixteen weeks in chronic model. Leukocyte patterns were evaluated in bronchoalveolar lavage (BAL). Both acute HP groups showed a higher number of total cells (p=0.0015 and p=0.0059), neutrophils (p=0.0002 and p<0.0001), eosinophils (p<0.0001 and p=0.0351), and lymphocytes (p=0.0070 and p<0.0001) in the BAL compared to control group. The acute HPA group exhibited a greater presence of eosinophils (p=0.0047) compared to the HPF group, while the acute HPF group had a higher number of neutrophils (p=0.0002) and lymphocytes (p=0.0463) compared to the acute HPA group. Both chronic HP groups had a higher number of total cells (p=0.0088 and p<0.0001), neutrophils (p=0.0037 and p<0.0001), eosinophils (p<0.0001 and p=0.0096) and lymphocytes (p=0.0016 and p<0.0001) in BAL compared to control group. In addition, chronic FHP showed more total cells (p=0.0001) than chronic AHP, more macrophages (p=0.0002 and p=0.0011) than control and chronic AHP and more neutrophils (p=0.0476) and lymphocytes (p=0.0083) than chronic AHP. A different cellular response was observed in the BAL depending on the causative antigen. In avian-induced HP, eosinophils appear to play a more significant role, whereas in fungal-induced HP, neutrophils and lymphocytes were more prevalent. This suggests that during the inflammatory phase of HP, two distinct immune responses could develop depending on the causative agent.