Urban Particulate Matter (PM10) Induces a Distinct and Complex Programme of Activation in Human Dendritic Cells

Fossil fuel derived particulate matter (PM) is present within airway myeloid cells of individuals exposed to urban pollution and is linked with inflammatory disease. We hypothesized that exposure of airway dendritic cells (DC) to PM enhances their ability to induce inflammatory responses. We examined the effects of urban ambient PM of different sizes (<10μm, PM10; <2.5μm, PM2.5) on human DC, differentiated from monocytes (MoDC) or FACS-sorted (HLA-DR+Lin- cells which express ZBTB46) from induced sputum cells (RT-DC). DC phenotype was assessed by flow cytometry and qRT-PCR; stimulatory capacity determined in a mixed leukocyte reaction.

PM10 from two UK locations induced 'classical' MoDC maturation indicated by dose-dependent up-regulation of MHC class II, CD40, CD86 and CCR7. Neither PM2.5 nor carbon black particles, representing the particulate core of PM, activated DC. Consistent with their more mature phenotype, PM10 treated MoDC were significantly more stimulatory for naive CD4+ T cells. Like the TLR4 agonist LPS, PM10 induced MoDC production of IL-6, and IL-12 but in contrast to LPS, PM10 also induced the release of cytokines associated with inflammasome activation (IL-1β and IL-18) as well as IL-23. Unlike LPS, PM10 additionally induced aryl hydrocarbon receptor (AhR) signalling in MoDC, as indicated by AhR-dependent induction of the target gene CYP1A1. PM10 also induced CYP1A1 expression by RT-DCs in vitro. 

Thus, components of urban PM10 induce a complex programme of DC activation that includes classical maturation, inflammasome dependent cytokine release and AhR signalling. In the airway, such changes may lead to altered responses to inhaled antigen.