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

Williams, Marc A.; Porter, Michael D.; Horton, Maureen R.; Guo, Jia; Roman, Jessica; Williams, D'Ann; Breysse, Patrick N.; Georas, Steve N.

doi:10.1016/j.jaci.2006.10.022

Cited by 55 publications

(62 citation statements)

References 39 publications

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“…Particles used in this study were concentrated environmental APM collected from Baltimore City air and environmental DEP collected from the diesel exhaust plenums of the Baltimore Harbor Tunnel (using a cyclone collector with a cut-size of 0.3 m that collected particles greater than 0.1-0.3 m in aerodynamic diameter) as described [5,6,19] . Environmental DEP was collected at a flow rate of 1.0 m 3 /min from the section of the tunnel used by truck traffic, creating a PM sample enriched in diesel particles and collected over a period of 1 month.…”

Section: Particle Collection and Preparationmentioning

confidence: 99%

“…secretion of interferon-␥ , IFN-␥ ) in asthma [5,6] . Environmental cues such as ambient particulate matter (APM) and diesel exhaust particles (DEP, an emission source PM) stimulate adaptive and innate immunity in asthma [3,[5][6][7][8][9] . The modulation of lung innate immunity by biologically, chemically or structurally disparate particulate matter (PM) species that can breach the airway barrier and interact with host immunity is important.…”

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confidence: 99%

“…We have shown that APM, environmental DEP or a common allergen (e.g. ragweed extract) instructs 'non-classic' DC maturation enabling them to stimulate a complex pattern of Th1-and Th2-associated responses [6,12,18,19] . The exact location of where DCs sample respirable antigen in the lung remains ill-defined [15,16] , although it is known that DC serve a key role in the immune pathology of allergic asthma [20][21][22] .…”

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confidence: 99%

“…Studies exploring the role of DC activation and allergic risk in asthma development have focused on the adjuvant potential of PM to induce allergic sensitization to a coadministered antigen-like ovalbumin (OVA) or house dust mite [6,12,18,[28][29][30][31][32] . Often high and repeated doses of PM exposure are used that also induce tissue damage and general airway inflammation.…”

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confidence: 99%

“…We have previously conducted detailed in vitro studies of the effects of PM on human and murine mDC [5,6,12,19] . Until now, we have not tested the acute immunological and inflammatory effects of APM in vivo to model the immunological effects of an acute exposure to PM in naïve mice.…”

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confidence: 99%

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Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

et al. 2010

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The biological effects of acute particulate air pollution exposure in host innate immunity remain obscure and have relied largely on in vitro models. We hypothesized that single acute exposure to ambient or engineered particulate matter (PM) in the absence of other secondary stimuli would activate lung dendritic cells (DC) in vivo and provide information on the early immunological events of PM exposure and DC activation in a mouse model naïve to prior PM exposure. Activation of purified lung DC was studied following oropharyngeal instillation of ambient particulate matter (APM). We compared the effects of APM exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and silver nanoparticles (AgP). We found that PM species induced variable cellular infiltration in the lungs and only APM exposure induced eosinophilic infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type cytokine response from naïve CD4+ T cells ex vivo. Cultures of primary peribronchial lymph node cells from mice exposed to APM and DEP also displayed a Th2-type immune response ex vivo. We conclude that exposure of the lower airway to various PM species induces differential immunological responses and immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness.

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Section: Particle Collection and Preparationmentioning

confidence: 99%