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TLR9 and IL-1R1 Promote Mobilization of Pulmonary Dendritic Cells during Beryllium Sensitization
- Source :
- The Journal of Immunology. 201:2232-2243
- Publication Year :
- 2018
- Publisher :
- The American Association of Immunologists, 2018.
-
Abstract
- Metal-induced hypersensitivity is driven by dendritic cells (DCs) that migrate from the site of exposure to the lymph nodes, upregulate costimulatory molecules, and initiate metal-specific CD4+ T cell responses. Chronic beryllium disease (CBD), a life-threatening metal-induced hypersensitivity, is driven by beryllium-specific CD4+ Th1 cells that expand in the lung-draining lymph nodes (LDLNs) after beryllium exposure (sensitization phase) and are recruited back to the lung, where they orchestrate granulomatous lung disease (elicitation phase). To understand more about how beryllium exposures impact DC function during sensitization, we examined the early events in the lung and LDLNs after pulmonary exposure to different physiochemical forms of beryllium. Exposure to soluble or crystalline forms of beryllium induced alveolar macrophage death/release of IL-1α and DNA, enhanced migration of CD80hi DCs to the LDLNs, and sensitized HLA-DP2 transgenic mice after single low-dose exposures, whereas exposures to insoluble particulate forms beryllium did not. IL-1α and DNA released by alveolar macrophages upregulated CD80 on immature BMDC via IL-1R1 and TLR9, respectively. Intrapulmonary exposure of mice to IL-1R and TLR9 agonists without beryllium was sufficient to drive accumulation of CD80hi DCs in the LDLNs, whereas blocking both pathways prevented accumulation of CD80hi DCs in the LDLNs of beryllium-exposed mice. Thus, in contrast to particulate forms of beryllium, which are poor sensitizers, soluble or crystalline forms of beryllium promote death of alveolar macrophages and their release of IL-1α and DNA, which act as damage-associated molecular pattern molecules to enhance DC function during beryllium sensitization.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
Enzyme-Linked Immunospot Assay
T cell
Immunology
chemistry.chemical_element
Lymphocyte Activation
Article
Berylliosis
Mice
03 medical and health sciences
Cell Movement
Hypersensitivity
medicine
Animals
Humans
Immunology and Allergy
Lung
Cells, Cultured
Sensitization
Mice, Knockout
Receptors, Interleukin-1 Type I
TLR9
Cell Differentiation
Dendritic Cells
Allergens
respiratory tract diseases
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
chemistry
Toll-Like Receptor 9
Chronic Disease
Myeloid Differentiation Factor 88
Cancer research
Alveolar macrophage
Immunization
Beryllium
CD80
Beryllium Disease
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 201
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....a3cab3baebb0d347505251516f91c318