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ToxSci Advance Access published online on August 17, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi279
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received April 14, 2005
Accepted June 26, 2005

Environmental Toxicology

Sustained Effect of Inhaled Diesel Exhaust Particles on T Lymphocyte-Mediated Immune Responses Against Listeria Monocytogenes

Xuejun J. Yin 1, Caroline C. Dong 1, Jane Y. C. Ma 2, James M. Antonini 2, Jenny R. Roberts 2, Mark W. Barger 2, and Joseph K. H. Ma 1*

1 School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506
2 Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505

* To whom correspondence should be addressed.
Joseph K. H. Ma, E-mail: jma{at}hsc.wvu.edu


  Abstract

Studies have shown that exposure to diesel exhaust particles (DEP) suppresses pulmonary host defense against bacterial infection. The present study was carried out to characterize whether DEP exposure exerts a sustained effect in which inhaled DEP increase the susceptibility of the lung to bacterial infection occurring at a later time. Brown Norway rats were exposed to filtered air or DEP by inhalation at a dose of 21.2 ± 2.3 mg/m3, 4 h/day for 5 days, and intratracheally instilled with saline or 100,000 Listeria monocytogenes (Listeria) 7 days after the final DEP exposure. Bacterial growth and cellular responses to DEP and Listeria exposures were examined at 3 and 7 days post-infection. The results showed that inhaled DEP prolonged the growth of bacteria, administered 7 days post DEP exposure, in the lung as compared to the air-exposed controls. Pulmonary responses to Listeria infection were characterized by increased production of interleukin (IL)-1{beta}, tumor necrosis factor (TNF)-{alpha}, IL-12, and IL-10 by alveolar macrophages (AM) and increased presence of T lymphocytes and their CD4+ and CD8+ subsets in lung draining lymph nodes that secreted elevated levels of IL-2, IL-6, IL-10, and interferon (IFN)-{gamma}. DEP were found to inhibit Listeria-induced production of IL-1{beta} and TNF-{alpha}, which are responsible for the innate immunity, and IL-12, which initiates the development of T helper (Th)1 responses, but enhance Listeria-induced AM production of IL-10, which prolongs Listeria survival in these phagocytes. The dual action of DEP on AM production of IL-12 and IL-10 correlated to an inhibition of the development of bacteria-specific T lymphocytes by DEP. Cytokine production by lymphocytes from DEP- and Listeria-exposed rats showed a marked decrease in the production of IL-2, IL-10, and IFN-{gamma} compared to Listeria infection alone, suggesting that either DEP inhibit the production of cytokines by lymphocytes or these lymphocytes contained T cell subsets that are different from those of Listeria infection alone and less effective in mediating Th1 immune responses. This study demonstrates that inhaled DEP, after a 7 day resting period, increase the susceptibility of the lung to bacterial infection occurring at a later time by inhibiting macrophage immune function and suppressing the development of T cell-mediated immune responses. The results support the epidemiological observations that exposure to DEP may be responsible for the pulmonary health effects on humans.

Keywords: diesel exhaust particles; host defense; Listeria monocytogenes; alveolar macrophages; T lymphocytes.
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