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. 2003 Apr;111(4):524–530. doi: 10.1289/ehp.5709

Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEPs). II. Effects of DEPs on T-cell-mediated immune responses in rats.

Xue-Jun Yin 1, Rosana Schafer 1, Jane Y C Ma 1, James M Antonini 1, Jenny R Roberts 1, David N Weissman 1, Paul D Siegel 1, Joseph K H Ma 1
PMCID: PMC1241439  PMID: 12676610

Abstract

Previously, we showed that diesel exhaust particles (DEPs) suppressed pulmonary clearance of Listeria monocytogenes (Listeria) and inhibited the phagocytosis of alveolar macrophages and their response to Listeria in the secretion of interleukin (IL)-1 beta, tumor necrosis factor alpha, and IL-12. In this report we examined the effects of DEPs and/or Listeria on T-cell development and secretion of IL-2, IL-6, and interferon (IFN)-gamma. We exposed Brown Norway rats to clean air or DEPs at 50 or 100 mg/m3 for 4 hr by nose-only inhalation and inoculated with 100,000 Listeria. Lymphocytes in the lung-draining lymph nodes were isolated at 3 and 7 days postexposure, analyzed for CD4+ and CD8+ cells, and measured for cytokine production in response to concanavalin A or heat-killed L. monocytogenes. Listeria infection induced lymphocyte production of IL-6. At 7 days postinfection, lymphocytes from Listeria-infected rats showed significant increases in CD4+ and CD8+ cell counts and the CD8+/CD4+ ratio and exhibited increased production of IFN-gamma and IL-2 receptor expression compared with the noninfected control. These results suggest an immune response that involves the action of IL-6 on T-cell activation, yielding Listeria-specific CD8+ cells. DEP exposure alone enhanced lymphocyte production of both IL-2 and IL-6 but inhibited lymphocyte secretion of IFN-gamma. In rats exposed to 100 mg/m3 DEPs and Listeria, a 10-fold increase occurred in pulmonary bacterial count at 3 days postinfection when compared with the Listeria-only exposure group. The isolated lymphocytes showed a significant increase in the CD4+ and CD8+ cell counts and the CD8+/CD4+ ratio and exhibited increased IL-2 responsiveness and increased capacity in the secretion of IL-2, IL-6, and IFN-gamma. This T-cell immune response was sufficient to allow the Brown Norway rats to clear the bacteria at 7 days postinfection and overcome the down-regulation of the innate immunity by the acute DEP exposure.

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Selected References

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  1. Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
  2. Antonini J. M., Yang H. M., Ma J. Y., Roberts J. R., Barger M. W., Butterworth L., Charron T. G., Castranova V. Subchronic silica exposure enhances respiratory defense mechanisms and the pulmonary clearance of Listeria monocytogenes in rats. Inhal Toxicol. 2000 Nov;12(11):1017–1036. doi: 10.1080/08958370050164635. [DOI] [PubMed] [Google Scholar]
  3. Chan T. L., Lee P. S., Hering W. E. Deposition and clearance of inhaled diesel exhaust particles in the respiratory tract of Fischer rats. J Appl Toxicol. 1981 Apr;1(2):77–82. doi: 10.1002/jat.2550010206. [DOI] [PubMed] [Google Scholar]
  4. Diaz-Sanchez D., Dotson A. R., Takenaka H., Saxon A. Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms. J Clin Invest. 1994 Oct;94(4):1417–1425. doi: 10.1172/JCI117478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Déry R. E., Bissonnette E. Y. IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions. Am J Respir Cell Mol Biol. 1999 Mar;20(3):407–412. doi: 10.1165/ajrcmb.20.3.3252. [DOI] [PubMed] [Google Scholar]
  6. Ford H. R., Hoffman R. A., Wang S., Simmons R. L. Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6. J Pediatr Surg. 1991 Apr;26(4):397–400. doi: 10.1016/0022-3468(91)90985-3. [DOI] [PubMed] [Google Scholar]
  7. Fujimaki H., Saneyoshi K., Shiraishi F., Imai T., Endo T. Inhalation of diesel exhaust enhances antigen-specific IgE antibody production in mice. Toxicology. 1997 Jan 15;116(1-3):227–233. doi: 10.1016/s0300-483x(96)03539-1. [DOI] [PubMed] [Google Scholar]
  8. Goossens P. L., Montixi C., Saron M. F., Rodriguez M., Zavala F., Milon G. Listeria monocytogenes: a live vector able to deliver heterologous protein within the cytosol and to drive a CD8 dependent T cell response. Biologicals. 1995 Jun;23(2):135–143. doi: 10.1006/biol.1995.0024. [DOI] [PubMed] [Google Scholar]
  9. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
  10. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  11. Kaempfer R. Regulation of the human interleukin-2/interleukin-2 receptor system: a role for immunosuppression. Proc Soc Exp Biol Med. 1994 Jul;206(3):176–180. doi: 10.3181/00379727-206-43737. [DOI] [PubMed] [Google Scholar]
  12. Kaufmann S. H., Flesch I. E. Cytokines in antibacterial resistance: possible applications for immunomodulation. Lung. 1990;168 (Suppl):1025–1032. doi: 10.1007/BF02718240. [DOI] [PubMed] [Google Scholar]
  13. Kaufmann S. H. Immunity to intracellular bacteria. Annu Rev Immunol. 1993;11:129–163. doi: 10.1146/annurev.iy.11.040193.001021. [DOI] [PubMed] [Google Scholar]
  14. Leong B. K., Coombs J. K., Sabaitis C. P., Rop D. A., Aaron C. S. Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J Appl Toxicol. 1998 Mar-Apr;18(2):149–160. doi: 10.1002/(sici)1099-1263(199803/04)18:2<149::aid-jat490>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  15. Lotz M., Jirik F., Kabouridis P., Tsoukas C., Hirano T., Kishimoto T., Carson D. A. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. doi: 10.1084/jem.167.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCormack J. M., Moore S. C., Gatewood J. W., Walker W. S. Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells. Cell Immunol. 1992 Dec;145(2):359–371. doi: 10.1016/0008-8749(92)90338-p. [DOI] [PubMed] [Google Scholar]
  17. Mielke M. E., Peters C., Hahn H. Cytokines in the induction and expression of T-cell-mediated granuloma formation and protection in the murine model of listeriosis. Immunol Rev. 1997 Aug;158:79–93. doi: 10.1111/j.1600-065x.1997.tb00994.x. [DOI] [PubMed] [Google Scholar]
  18. North R. J., Dunn P. L., Conlan J. W. Murine listeriosis as a model of antimicrobial defense. Immunol Rev. 1997 Aug;158:27–36. doi: 10.1111/j.1600-065x.1997.tb00989.x. [DOI] [PubMed] [Google Scholar]
  19. Park A. Y., Scott P. Il-12: keeping cell-mediated immunity alive. Scand J Immunol. 2001 Jun;53(6):529–532. doi: 10.1046/j.1365-3083.2001.00917.x. [DOI] [PubMed] [Google Scholar]
  20. Reasor M. J., McCloud C. M., DiMatteo M., Schafer R., Ima A., Lemaire I. Effects of amiodarone-induced phospholipidosis on pulmonary host defense functions in rats. Proc Soc Exp Biol Med. 1996 Apr;211(4):346–352. doi: 10.3181/00379727-211-43979. [DOI] [PubMed] [Google Scholar]
  21. Renauld J. C., Vink A., Van Snick J. Accessory signals in murine cytolytic T cell responses. Dual requirement for IL-1 and IL-6. J Immunol. 1989 Sep 15;143(6):1894–1898. [PubMed] [Google Scholar]
  22. Smith K. A. Interleukin-2. Curr Opin Immunol. 1992 Jun;4(3):271–276. doi: 10.1016/0952-7915(92)90076-q. [DOI] [PubMed] [Google Scholar]
  23. Soussi N., Milon G., Colle J. H., Mougneau E., Glaichenhaus N., Goossens P. L. Listeria monocytogenes as a short-lived delivery system for the induction of type 1 cell-mediated immunity against the p36/LACK antigen of Leishmania major. Infect Immun. 2000 Mar;68(3):1498–1506. doi: 10.1128/iai.68.3.1498-1506.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251–276. doi: 10.1146/annurev.iy.13.040195.001343. [DOI] [PubMed] [Google Scholar]
  25. Twigg H. L., 3rd Pulmonary host defenses. J Thorac Imaging. 1998 Oct;13(4):221–233. doi: 10.1097/00005382-199810000-00003. [DOI] [PubMed] [Google Scholar]
  26. Weiskirch L. M., Paterson Y. Listeria monocytogenes: a potent vaccine vector for neoplastic and infectious disease. Immunol Rev. 1997 Aug;158:159–169. doi: 10.1111/j.1600-065x.1997.tb01002.x. [DOI] [PubMed] [Google Scholar]
  27. Yang H. M., Antonini J. M., Barger M. W., Butterworth L., Roberts B. R., Ma J. K., Castranova V., Ma J. Y. Diesel exhaust particles suppress macrophage function and slow the pulmonary clearance of Listeria monocytogenes in rats. Environ Health Perspect. 2001 May;109(5):515–521. doi: 10.1289/ehp.01109515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yang H. M., Barger M. W., Castranova V., Ma J. K., Yang J. J., Ma J. Y. Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: evidence of DEP suppression of macrophage activity. J Toxicol Environ Health A. 1999 Nov 12;58(5):261–278. doi: 10.1080/009841099157232. [DOI] [PubMed] [Google Scholar]
  29. Yang H. M., Ma J. Y., Castranova V., Ma J. K. Effects of diesel exhaust particles on the release of interleukin-1 and tumor necrosis factor-alpha from rat alveolar macrophages. Exp Lung Res. 1997 May-Jun;23(3):269–284. doi: 10.3109/01902149709087372. [DOI] [PubMed] [Google Scholar]
  30. Yin Xue-Jun, Schafer Rosana, Ma Jane Y. C., Antonini James M., Weissman David D., Siegel Paul D., Barger Mark W., Roberts Jenny R., Ma Joseph K-H. Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEPs). I. Effects of DEPs on early pulmonary responses. Environ Health Perspect. 2002 Nov;110(11):1105–1111. doi: 10.1289/ehp.021101105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoshino S., Sagai M. Enhancement of collagen-induced arthritis in mice by diesel exhaust particles. J Pharmacol Exp Ther. 1999 Aug;290(2):524–529. [PubMed] [Google Scholar]
  32. Yu C. P., Yoon K. J. Retention modeling of diesel exhaust particles in rats and humans. Res Rep Health Eff Inst. 1991 May;(40):1–24. [PubMed] [Google Scholar]

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