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Abstract
Epidemiological studies have shown that desert dust exposure affects respiratory health. We aimed to investigate the NLRP3 inflammasome-caspase-1 pathway-dependent inflammatory properties of Saharan dust (SD) in a macrophage model and an air-liquid interface (ALI) co-culture model of the alveolar epithelium. Under submerged conditions wild-type (WT) and NLRP3-/- THP-1 cells were exposed to SD at 50 µg/cm². Using a Vitrocell® Cloud, A549/THP-1 WT ALI co-cultures were exposed to SD or DQ12 quartz at non-cytotoxic concentrations of 10, 20, and 30 µg/cm². Additionally, ALI co-cultures containing NLRP3-/- or CASPASE1/- THP-1 cells were exposed to SD. SD was found to contain endotoxin, and caused manifold higher interleukin (IL)-1β secretion in WT than in NLRP3/- THP-1 cells. Baked SD (220°C, overnight) induced IL-1β secretion to a ~4-fold lower extent. Co-exposure to baked SD and endotoxin synergistically restored the IL-1β secretion. In ALI co-cultures SD but not DQ12 upregulated the expression and secretion of IL-1β, IL-6, IL-8, and tumor necrosis factor α. The secretion of these cytokines was strongly decreased in co-cultures with CASPASE1/- or NLRP3/- THP-1 cells. The screening of multiple SD samples on WT THP-1 cells revealed that their inflammatory potencies strongly depended on the sampling day and location. The surprisingly strong SD-mediated activation of the NLRP3 inflammasome emphasizes its hazardousness and the need for risk mitigation strategies. Therefore, the connection between the toxicity of SD and its composition, especially its microbial components, needs to be further unraveled.
Supported by the Leibniz Collaborative Excellence Programme project DUSTRISK.

Abstract
A growing number of epidemiological studies has linked exposure to traffic-related air pollution (TRAP) to neurological and neurodegenerative diseases. In a previous study, we showed that subchronic inhalation exposure to diesel engine exhaust, as a model of TRAP, aggravates amyloid-β plaque formation and motor function impairment in the 5xFAD transgenic mouse model of Alzheimer's disease (AD). To further strengthen the epidemiological association between TRAP and AD we exposed 5xFAD and wildtype littermate mice for 5 h/day, 5 days/week during 2 or 4 consecutive weeks at a representative urban traffic-dominated location to: (I) concentrated ambient particles, (II) particle filtered ambient air or (III) clean air (control). Our study revealed that repeated inhalation exposure to TRAP accelerates plaque formation in the 5xFAD mice. Data also indicated that the gaseous fraction of the air pollutant mixture probably plays only a minor role in this effect. The major outcome of this study substantiates the role of air pollution in AD and suggests that long-term exposure to traffic-related air pollution particles is a risk factor for this debilitating disease.
Acknowledgements: The work leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 814978 (TUBE) and a cross-border grant awarded by the Alzheimer Forschung Initiative (AFI, Germany) and Alzheimer Nederland.