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)-1beta,
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.
Diesel exhaust particles were found to inhibit Listeria-induced production of IL-1beta 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 with 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 either that
DEP inhibit the production of
cytokines by lymphocytes or that 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.