Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells.

Abstract

Dendritic cells (DCs) translate environmental cues into T-cell activating signals, and are centrally involved in allergic airway inflammation. Ambient particulate matter (APM) is ubiquitous and associated with allergic diseases, but it is unknown whether APM directly activates DCs. To study comprehensively the effects of APM on myeloid DC phenotype and function. Development of DC was modeled using human CD34(+) progenitor cells. APM was collected from ambient outdoor air in Baltimore city. We studied the effects of APM on DC activation in vitro, compared with LPS. Ambient particulate matter enhanced DC expression of costimulatory receptors but suppressed the expression of both the endocytosis receptor CD206 and uptake of fluorescein isothiocyanate-conjugated dextran. The expression of the Toll-like pattern-recognition receptors Toll-like receptor 2 and Toll-like receptor 4 was also blunted. APM-exposed DCs secreted less IL-12 and IL-6 but exhibited increased secretion of IL-18 and IL-10 compared with LPS stimulation. A T(H)2-like pattern of cytokine production was seen in cocultures of APM-stimulated DCs and alloreactive naive CD4(+) T cells where the IL-13 to IFN-gamma ratio was reversed. This contrasted with the T(H)1 polarizing effects of LPS on DCs. We report for the first time that APM-exposed DCs direct a complex T(H)1/T(H)2-like pattern of T-cell activation by mechanisms that involve nonclassic activation of DCs. Inhaled APM can act directly on DCs as a danger signal to direct a proallergic pattern of innate immune activation.