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

Etsushi Kuroda et al., 2016, Immunity 45, 1299–1310

Speaker: Sung-Lin Liu (劉松林)                                          Time: 13:10~14:00, May. 3.2017

Commentator: Dr. Wang, Jiu-Yao (王志堯 老師)              Place: Room 601

Abstract:

Particulates less than 2.5 μm in diameter may cause lung inflammation and enhance allergic responses.  Inducible bronchus-associated lymphoid tissues (iBALTs) are induced in the lung by chronic inflammation in human patients. However, whether iBALT formation plays an important role in particulate-enhanced allergen-specific type 2 immune response is unknown. In this study, the authors hypothesized that particulates cause iBATLs formation that may enhance allergic responses.  In order to observe iBATL formation in particulate-enhanced allergen responses, the authors established an OVA-induced lung inflammation model using the instillation of OVA with alum stimulation.  First, the authors used particulate alum to stimulate isolated alveolar macrophage (AM) and mice.  They found alum induce AM death and IL-1α release in vitro and in vivo.  Second, the authors compared iBALT formation in OVA-induced mice with or without alum stimulation.  They found alum-induced AM release IL-1α that enhances iBALT formation. Third, the authors used OVA-induced conditioned knockout mice which transform diphtheria toxin receptor in CD11c cell and lack Bcl6 gene in CD4 cell to show that alum induces IL-1α release from dying AM and induce iBATLs formation. This process was depends on dendritic cell and T_fh cell.  They also injected alum from different routes and showed that the process of IL-1α release and iBALT formation was a local immune response specific for the lung.  This novel pathway induced by fine particles may provide a therapeutic strategy for prevention and treatment of particulates-enhanced allergic diseases.

References:

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