| Autor: |
Chattoraj, Sangbrita S., Murthy, Rachana, Ganesan, Shyamala, Goldberg, Joanna B., Zhao, Ying, Hershenson, Marc B., Sajjan, Umadevi S. |
| Zdroj: |
Infection and Immunity; March 2010, Vol. 78 Issue: 3 p984-993, 10p |
| Abstrakt: |
ABSTRACTPseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF) patients, facilitates infection by other opportunistic pathogens. Burkholderia cenocepacia, which normally infects adolescent patients, encounters alginate elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosaalginate facilitates B. cenocepaciainfection in mice, cystic fibrosis transmembrane conductance regulator knockout mice were infected with B. cenocepaciastrain BC7 suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosaalginate (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored. Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate showed persistence of bacteria and increased cytokine levels for up to 7 days. Histological examination of the lungs indicated that there was moderate to severe inflammation and pneumonic consolidation in isolated areas at 5 and 7 days postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis of B. cenocepaciaby professional phagocytes both in vivoand in vitro. P. aeruginosaalginate also reduced the proinflammatory responses of CF airway epithelial cells and alveolar macrophages to B. cenocepaciainfection. The observed effects are specific to P. aeruginosaalginate, because enzymatically degraded alginate or other polyuronic acids did not facilitate bacterial persistence. These observations suggest that P. aeruginosaalginate may facilitate B. cenocepaciainfection by interfering with host innate defense mechanisms. |
| Databáze: |
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