Inhaled Fine Particles Induce Alveolar Macrophage Death And Interleukin-1 Alpha Release To Promote Inducible Bronchus-Associated Lymphoid Tissue Formation

Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1 alpha (IL-1 alpha) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1 alpha release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1 alpha release and iBALT formation, even long after particulate instillation. Recombinant IL-1 alpha was sufficient to induce iBALTs, which coincided with subsequent immunoglobulin E responses, and IL-1-receptor-deficient mice failed to induce iBALT formation. Therefore, the AM-IL-1 alpha-iBALT axis might be a therapeutic target for particulate-induced allergic inflammation.