Abstract:
:Beryllium exposure results in beryllium hypersensitivity in a subset of exposed individuals, leading to granulomatous inflammation and fibrosis in the lung. In addition to its antigenic properties, beryllium has potent adjuvant activity that contributes to sensitization via unknown pathways. Here we show that beryllium induces cellular death and release of interleukin (IL)-1α and DNA into the lung. Release of IL-1α was inflammasome independent and required for beryllium-induced neutrophil recruitment into the lung. Beryllium enhanced classical dendritic cell (cDC) migration from the lung to draining lymph nodes (LNs) in an IL-1R-independent manner, and the accumulation of activated cDCs in the LN was associated with increased priming of CD4(+) T cells. DC migration was reduced in Toll-like receptor 9 knockout (TLR9KO) mice; however, cDCs in the LNs of TLR9-deficient mice were highly activated, suggesting a role for more than one innate receptor in the effects on DCs. The adjuvant effects of beryllium on CD4(+) T-cell priming were similar in wild-type, IL-1R-, caspase-1-, TLR2-, TLR4-, TLR7-, and TLR9-deficient mice. In contrast, DC migration, activation, and the adjuvant effects of beryllium were significantly reduced in myeloid differentiation primary response gene 88 knockout (MyD88KO) mice. Collectively, these data suggest that beryllium exposure results in the release of damage-associated molecular patterns that engage MyD88-dependent receptors to enhance pulmonary DC function.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
McKee AS,Mack DG,Crawford F,Fontenot APdoi
10.1038/mi.2015.14subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1237-47issue
6eissn
1933-0219issn
1935-3456pii
mi201514journal_volume
8pub_type
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