ToxSci Advance Access originally published online on December 2, 2003
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Toxicological Sciences 77, 263-271 (2004)
Copyright © 2004 by the Society of Toxicology
ENVIRONMENTAL TOXICOLOGY |
Suppression of Cell-Mediated Immune Responses to Listeria Infection by Repeated Exposure to Diesel Exhaust Particles in Brown Norway Rats
* School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506;
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
Mechanical and Aerospace Engineering Department, West Virginia University, Morgantown, West Virginia 26506; and
School of Medicine, West Virginia University, Morgantown, West Virginia 26506
Diesel exhaust particles (DEP) have been shown to alter pulmonary immune responses to bacterial infection. Exposure of rats to 100 mg/m3 DEP for 4 h was found to aggravate Listeria monocytogenes(Listeria) infection at 3 days postinfection, but the bacteria were largely cleared at 7 days postinfection due to the development of a strong T cell–mediated immunity. In the present study, we examined the effects of repeated DEP exposure at lower doses on pulmonary responses to bacterial infection. Brown Norway rats were exposed to DEP by inhalation at 20.62 ± 1.31 mg/m 3 for 4 h/day for 5 days, followed by intratracheal inoculation with 100,000 Listeria at 2 h after the last DEP exposure. DEP-exposed rats showed a significant increase in lung bacterial load at both 3 and 7 days postinfection. The repeated DEP exposure was shown to suppress both the innate, orchestrated by alveolar macrophages (AM), and T cell–mediated responses to Listeria. DEP inhibited AM production of interleukin- (IL-) 1ß, tumor necrosis factor- (TNF-) 
, and IL-12 but enhanced Listeria-induced AM production of IL-10, which has been shown to prolong the survival of intracellular pathogens such as Listeria. DEP exposure also suppressed the development of bacteria-specific lymphocytes from lung-draining lymph nodes, as indicated by the decreased numbers of T lymphocytes and their CD4+ and CD8+ subsets. Furthermore, the DEP exposure markedly inhibited the Listeria-induced lymphocyte secretion of IL-2 at day 7, IL-10 at days 3 and 7, and interferon- (IFN-) 
at days 3 to 10 postinfection when compared to air-exposed controls. These results show a sustained pattern of downregulation of T cell–mediated immune responses by repeated low-dose DEP exposure, which is different from the results of a single high-dose exposure where the acute effect of DEP aggravated bacteria infection but triggered a strong T cell–mediated immunity.
Key Words: diesel exhaust particles; inhalation; Listeria monocytogenes; alveolar macrophages; lymphocytes; cytokines.
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