Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation

Immunity. 2016 Dec 20;45(6):1299-1310. doi: 10.1016/j.immuni.2016.11.010.


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-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α 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-1α release and iBALT formation, even long after particulate instillation. Recombinant IL-1α 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-1α-iBALT axis might be a therapeutic target for particulate-induced allergic inflammation.

Keywords: IL-1α; IgE; Particulate; alveolar macrophages; iBALT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Compounds / toxicity
  • Animals
  • Bronchi / immunology*
  • Female
  • Interleukin-1alpha / immunology*
  • Lymphoid Tissue / immunology*
  • Macrophages, Alveolar / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Particulate Matter / toxicity*
  • Silicon Dioxide / toxicity


  • Aluminum Compounds
  • Interleukin-1alpha
  • Particulate Matter
  • Silicon Dioxide