title: Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To study comprehensively the effects of APM on myeloid DC phenotype and function.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Inhaled APM can act directly on DCs as a danger signal to direct a proallergic pattern of innate immune activation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. marc_williams@urmc.rochester.edu <marc_williams@urmc.rochester.edu>
authors.forename: Marc A
authors.initials: MA
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Porter
authors.forename: Maureen
authors.initials: M
authors.lastname: Horton
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Jessica
authors.initials: J
authors.lastname: Roman
authors.forename: D'Ann
authors.initials: D
authors.lastname: Williams
authors.forename: Patrick
authors.initials: P
authors.lastname: Breysse
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
mesh_terms: D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000502:physiology*; D004705:Endocytosis; D006801:Humans; D037181:Lectins, C-Type / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D052638:Particulate Matter / Q000633:toxicity*; D011956:Receptors, Cell Surface / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D052638:Particulate Matter; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D017493:Leukocyte Common Antigens