MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4⁺ T-cell priming

Mucosal Immunology
A S McKeeAndrew P Fontenot

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 myeloi...Continue Reading

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Citations

Oct 30, 2016·Current Opinion in Immunology·Amy S McKee, Andrew P Fontenot
Apr 21, 2018·Annals of the American Thoracic Society·Andrew P Fontenot
Feb 6, 2018·Annual Review of Immunology·Antonio J Pagán, Lalita Ramakrishnan
Jun 27, 2018·Contact Dermatitis·Marian SzczepanikLi Wen
May 17, 2019·JCI Insight·Shaikh M AtifAndrew P Fontenot
Sep 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Morgan F WadeAmy S McKee
Dec 20, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew P FontenotAmy S McKee
Jan 18, 2018·Current Opinion in Allergy and Clinical Immunology·Anne E Wyman, Stella E Hines
Apr 8, 2020·Frontiers in Immunology·Sarah A GreavesAndrew P Fontenot
Feb 26, 2021·The Journal of Clinical Investigation·Michael T FaltaAndrew P Fontenot

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Methods Mentioned

BETA
bronchoalveolar lavage
flow cytometry
ELISA

Software Mentioned

GraphPad
Wallac 1420 Workstation
FACS Diva
FlowJo
Prism

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