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.
© 2010 S. Karger AG, Basel
- Innate immunity
- Allergic immunity
- Dendritic cell
- Particulate matter
- Cohn L, Elias JA, Chupp GL: Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 2004;22:789–815.
- Galli SJ, Tsai M, Piliponsky AM: The development of allergic inflammation. Nature 2008;454:445–454.
- Nel AE, Diaz-Sanchez D, Ng D, Hiura T, Saxon A: Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. J Allergy Clin Immunol 2008;102:539–554.
- Wills-Karp M: Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999;17:255–281.
- Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, Breysse P, Georas SN, Williams MA: Diesel-enriched particulate matter functionally activates human dendritic cells. Am J Respir Cell Mol Biol 2007;37:706–719.
- Williams MA, Porter M, Horton M, Guo J, Roman J, Williams D, Breysse P, Georas SN: Ambient particulate matter directs nonclassic dendritic cell activation and a mixed T(H)1/T(H)2-like cytokine response by naive CD4(+) T cells. J Allergy Clin Immunol 2007;119:488–497.
- Miyabara Y, Ichinose T, Takano H, Lim HB, Sagai M: Effects of diesel exhaust on allergic airway inflammation in mice. J Allergy Clin Immunol 1998;102:805–812.
- Granum B, Løvik M: The effect of particles on allergic immune responses. Toxicol Sci 2002;65:7–17.
- Mamessier E, Nieves A, Vervloet D, Magnan A: Diesel exhaust particles enhance T-cell activation in severe asthmatics. Allergy 2006;61:581–588.
- Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutch WA: Role of free radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol 2001;14:1371–1377.
- Baulig A, Singh S, Marchand A, Schins R, Barouki R, Garlatti M, Marano F, Baeza-Squiban A: Role of Paris PM(2.5) components in the pro-inflammatory response induced in airway epithelial cells. Toxicology 2009;261:126–135.
- Williams MA, Rangasamy T, Bauer SM, Killedar S, Karp M, Kensler TW, Yamamoto M, Breysse P, Biswal S, Georas SN: Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J Immunol 2008;181:4545–4559.
- Kadiiska MB, Mason RP, Dreher KL, Costa DL, Ghio AJ: In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem Res Toxicol 2007;10:1104–1108.
- Becker S, Dailey LA, Soukup JM, Grambow SC, Devlin RB, Huang YC: Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress. Environ Health Perspect 2005;113:1032–1038.
- Blank F, Rothen-Rutishauser B, Gehr P: Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol 2007;36:669–677.
- Geiser M: Morphological aspects of particle uptake by lung phagocytes. Microsc Res Tech 2002;57:512–522.
- van Rijt LS, Lambrecht BN: Dendritic cells in asthma: a function beyond sensitization. Clin Exp Allergy 2005;35:1125–1134.
- Rangasamy T, Williams MA, Bauer S, Trush MA, Emo J, Georas SN, Biswal S: Nrf2 inhibits the maturation of murine dendritic cells by ragweed extract. Am J Respir Cell Mol Biol 2010;43:276–285.
- Williams MA, Cheadle C, Watkins T, Tailor A, Killedar SY, Breysse P, Barnes K, Georas SN: TLR2 and TLR4 as potential biomarkers of environmental particulate matter exposed human myeloid dendritic cells. Biomarker Insights 2007;2:225–239.
- Hammad HM, Kool M, Lambrecht BN: Role of airway dendritic cell subsets in asthma. Cytometry B Clin Cytom 2007;72B:120–121.
- Lambrecht BN, Salomon B, Klatzman D, Pauwels RA: Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 1998;160:4090–4097.
- Lanckacker EA, Robays LJ, Joos GF, Vermaelen KY: A new danger in the air: how pulmonary innate immunity copes with man-made airborne xenobiotics. J Innate Immun 2010;2:96–106.
- Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.
- Lambrecht BN, De Veerman M, Coyle AJ, Gutierrez-Ramos JC, Thielemans K, Pauwels RA: Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 2000;106:551–559.
- Oriss TB, Ostroukhova M, Seguin-Devaux C, Dixon-McCarthy B, Stolz DB, Watkins SC, Pillemer B, Ray P, Ray A: Dynamics of dendritic cell phenotype and interactions with CD4(+) T cells in airway inflammation and tolerance. J Immunol 2005;174:854–863.
- Vermaelen KY, Carro-Muino I, Lambrecht BN, Pauwels RA: Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J Exp Med 2001;193:51–60.
- Vermaelen K, Pauwels R: Pulmonary dendritic cells. Am J Respir Crit Care Med 2005;172:530–551.
- de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model. Toxicol Sci 2005;87:409–418.
- de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Clin Exp Allergy 2006;36:1469–1479.
- de Haar C, Kool M, Hassing I, Bol M, Lambrecht BN, Pieters R: Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity. J Allergy Clin Immunol 2008;121:1246–1254.
- de Heer HJ, Hammad H, Soullié T, Hijdra D, Vos N, Willart MA, Hoogsteden HC, Lambrecht BN: Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 2004;200:89–98.
- Ohtani T, Nakagawa S, Kurosawa M, Mizuashi M, Ozawa M, Aiba S: Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant response. J Immunol 2005;174:2412–2419.
- van Rijt LS, Jung S, Kleinjan A, Vos N, Willart M, Duez C, Hoogsteden HC, Lambrecht BN: In vivo depletion of lung CD11c (+) dendritic cells during allergen challenge abrogates the characteristic features of asthma. J Exp Med 2005;201:981–991.
- Feau S, Facchinetti V, Granucci F, Citterio S, Jarrossay D, Seresini S, Protti MP, Lanzavecchia A, Ricciardi-Castagnoli P: Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice. Blood 2005;105:697–702.
- Rothen-Rutishauser BM, Kiama SG, Gehr P: A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am J Respir Cell Mol Biol 2005;32:281–289.
- Robertson JM, Jensen PE, Evavold BD: DO11.10 and OT-II T cells recognize a C-terminal ovalbumin 323–339 epitope. J Immunol 2000;164:4706–4712.
- Dong W, Selgrade MJ, Gilmour MI: Systemic administration of Bordetella pertussis enhances pulmonary sensitization to house dust mite in juvenile rats. Toxicol Sci 2003;72:113–121.
- Stevens T, Krantz QT, Linak WP, Hester SA, Gilmour MI: Increased transcription of immune and metabolic pathways in naive and allergic mice exposed to diesel exhaust. Toxicol Sci 2008;102:359–370.
- Williams MA, Bauer S, Lu W, Guo J, Walter S, Bushnell TP, Lillehoj EP, Georas SN: Deletion of the mucin-like molecule Muc1 enhances dendritic cell activation in response to toll-like receptor ligands. J Innate Immun 2010;2:123–143.
- Blasius AL, Giurisat E, Cella M, Schreiber RD, Shaw AS, Colonna M: Bone marrow stromal cell antigen 2 is a specific marker of type I IFN producing cells in the naïve mouse, but a promiscuous cell surface antigen following IFN stimulation. J Immunol 2006;177:3260–3265.
- Hammad H, Lambrecht BN: Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 2006;118:331–336.
- Li N, Hao M, Phalen RF, Hinds WC, Nel AE: Particulate air pollutants and asthma – a paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin Immunol 2003;109:250–265.
- Shi Y, Rock KL: Cell death releases endogenous adjuvants that selectively enhance immune surveillance of particulate antigens. Eur J Immunol 2002;32:155–162.
- Kouro T, Takatsu K: IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol 2009;21:1303–1309.
- Percopo CM, Dyer KD, Killoran KE, Rosenberg HF: Isolation of human eosinophils: microbead method has no impact on IL-5 sustained viability. Exp Dermatol 2010;19:467–469.
- Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J, Capron A, Capron M: Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med 1994;179:703–708.
- Oberdorster G: Lung dosimetry – pulmonary clearance of inhaled particles. Aerosol Sci Technol 1993;18:279–289.
- Horner AA: Regulation of aeroallergen immunity by the innate immune system: laboratory evidence for a new paradigm. J Innate Immun 2010;2:107–112.
- Ng N, Lam D, Paulus P, Batzer G, Horner AA: House dust extracts have both Th2 adjuvant and tolerogenic activities. J Allergy Clin Immunol 2006;117:1074–1081.
- Lam D, Ng N, Lee S, Batzer G, Horner AA: Airway house dust extract exposures modify allergen-induced airway hypersensitivity responses by TLR4-dependent and independent pathways. J Immunol 2008;181:2925–2932.
- Diaz-Sanchez D, Riedl M: Diesel effects on human health: a question of stress? Am J Physiol Lung Cell Mol Physiol 2005;289:L722–L723.
- Holt PG, Schon-Hegrad MA, Oliver J, Holt BJ, McMenamin PG: A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium. Int Arch Allergy Appl Immunol 1990;91:155–159.
- Reibman J, Hsu Y, Chen LC, Bleck B, Gordon T: Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. Am J Respir Cell Mol Biol 2003;28:648–654.
- Baulig A, Garlatti M, Bonvallot V, Marchand A, Barouki R, Marano F, Baeza-Squiban A: Involvement of reactive oxygen species in the metabolic pathways triggered by diesel exhaust particles in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2003;285:L671–L679.
- Blanchet S, Ramgolam K, Baulig A, Marano F, Baeza-Squiban A: Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells. Am J Respir Cell Mol Biol 2004;30:421–427.
- Rumelhard M, Ramgolam K, Auger F, Dazy AC, Blanchet S, Marano F, Baeza-Squiban A: Effects of PM2.5 components in the release of amphiregulin by human airway epithelial cells. Toxicol Lett 2007;168:155–164.
- Bleck B, Tse DB, Jaspers I, Curotto de Lafaille MA, Reibman J: Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. J Immunol 2006;176:7431–7437.
- Bleck B, Tse DB, Curotto de Lafaille MA, Zhang F, Reibman J: Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation and polarization via thymic stromal lymphopoietin. J Clin Immunol 2008;28:147–156.
- Kumagai Y, Arimoto T, Shinyashiki M, Shimojo N, Nakai Y, Yoshikawa T, Sagai M: Generation of reactive oxygen species during interaction of diesel exhaust particle components with NADPH-cytochrome P450 reductase and involvement of bioactivation in the DNA damage. Free Radic Biol Med 1997;22:479–487.
- Headley MB, Zhou B, Shih WX, Aye T, Comeau MR, Ziegler SF: TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses. J Immunol 2009;182:1641–1647.
- Gehr P, Blank F, Rothen-Rutishauser VBM: Fate of inhaled particles after interaction with the lung surface. Paediatr Respir Rev 2006;7:S73–S75.
- Muller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B: Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J R Soc Interface 2010;7 (suppl 1):S27–S40.
- Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P: Dendritic cells express tight junctions and penetrate gut eptithelial monolayers to sample bacteria. Nat Immunol 2001;2:361–367.
- Sung SS, Fu SM, Rose CE Jr, Gaskin F, Ju ST, Beaty SR: A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J Immunol 2006;176:2161–2172.
- Braun A, Bewersdorff M, Lintelmann J, Matuschek G, Jakob T, Göttlicher M, Schober W, Buters JT, Behrendt H, Mempel M: Differential impact of diesel particle composition on pro-allergic dendritic cell function. Toxicol Sci 2010;113:85–94.
Dr. Marc Adrian Williams
NHEERL, Environmental Public Health Division, Cardiopulmonary and Immunotoxicology Branch, Office of Research and Development
US Environmental Protection Agency, Research Triangle Park, NC 27711 (USA)
Tel. +1 919 541 2255, E-Mail Williams.firstname.lastname@example.org
Received: August 16, 2010
Accepted after revision: October 6, 2010
Published online: November 23, 2010
Number of Print Pages : 17
Number of Figures : 7, Number of Tables : 1, Number of References : 65
Journal of Innate Immunity
Vol. 3, No. 2, Year 2011 (Cover Date: February 2011)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
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