Ozone-enhanced pulmonary infection with Streptococcus zooepidemicus in mice. The role of alveolar macrophage function and capsular virulence factors.
Ozone exposure has been shown to increase the susceptibility of mice to pulmonary bacterial infection. We report here the differences in susceptibility of two strains of mice (C3H/HeJ and C57Bl/6) to pulmonary challenge with Streptococcus zooepidemicus, and demonstrate an association between O3 exposure, reduced alveolar macrophage (AM) function, and increased mortality to infection. After a 3-h exposure to air or to 0.4 or 0.8 ppm O3, mice received an infection of bacteria by aerosol. Subsequent mortality observed over a 20-day period for any given exposure concentration was greater in the C3H/HeJ mice than in the C57Bl/6 mice. Phagocytosis assays identified the AM from O3-exposed lungs as having an impaired ability to engulf the bacteria. Baseline phagocytic activity in C3H/HeJ mice was lower than that in C57Bl/6 mice. Microbiologic assessment of the lungs at various times after infection revealed that the streptococci proliferated rapidly in the lungs of O3-exposed mice, grew more quickly upon isolation, and displayed a mucoid colony appearance indicative of increased encapsulation. In vitro assays confirmed that the encapsulated isolates prevented binding of the bacteria to AM, and reinfection of nonexposed mice with the encapsulated isolate resulted in increased mortality compared with infection with similar numbers of the original unencapsulated bacteria. We have demonstrated that O3 inhalation impairs AM activity in the lung. The streptococci are then able to proliferate and more fully express virulence factors, in particular, the antiphagocytic capsule, which prohibits the ingestion of bacteria by pulmonary phagocytes and leads to increased severity of infection.
Gilmour
M I
MI
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill.
Park
P
P
Selgrade
M K
MK
D000393:Air Pollutants / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D016667:Bacterial Capsules / Q000187:drug effects / Q000633:toxicity*; D016009:Chi-Square Distribution; D004198:Disease Susceptibility; D005260:Female; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013290:Streptococcal Infections / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D013291:Streptococcus / Q000187:drug effects / Q000472:pathogenicity*; D013997:Time Factors; D014774:Virulence / Q000187:drug effects
D000393:Air Pollutants; D010126:Ozone