Suppression of Cell-Mediated Immune Responses to Listeria Infection by Repeated Exposure to Diesel Exhaust Particles in Brown Norway Rats

Abstract

Diesel exhaust particles (DEP) have been shown to alter pulmonary immune responses to bacterial infection. Exposure of rats to 100 mg/m(3) 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-) 1beta, tumor necrosis factor- (TNF-) alpha, 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-) gamma 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.

Health effects of air pollution

“…17 Repeated low-dose DEP exposure resulted in downregulation of T cell-mediated immune responses, whereas a single high-dose exposure to DEPs aggravated bacterial infection and triggered strong T cell-mediated immunity, indicating that DEPs can also alter pulmonary immune responses to bacterial infection. 31 Individuals with gene variants for phase II detoxifying enzymes (glutathione-s-transferase P1 and M1), causing the absence or reduced production of these enzymes, have been demonstrated to have increased susceptibility …”

The effects of air pollution on the health of children

“…However, a study conducted in Chile by Ruiz et al (42) found no association between ambient air pollution and the humoral immune system in children. Emerging evidence from animal toxicological studies suggest that ambient air pollution may cause suppression of host immunity (43,44).…”

Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma

“…Although other inflammatory disorders, such as chronic alcoholism 5 and particulate matter inhalation, 6 have been linked with AM dysfunction, AM function has not been extensively evaluated in asthma. Recently, increased AM activation and decreased phagocytosis of apoptotic cells were reported in asthmatic adults.…”