A mouse model of resistance and susceptibility to a pulmonary infection with Pseudomonas aeruginosa (PA), was used to study the inflammatory profile early following infection. This study allowed the identification of the mechanisms responsible for the resistant phenotype. We have first determined the pivotal role of the neutrophil recruitment in the alveolar space in the host defense against PA. This influx occurred earlier in the resistant BALB/c mice than in susceptible DBA/2 mice and occurred concommitantly with the beginning of the bacterial clearance. Furthermore, levels of TNFalpha were found to be higher in BALB/c mice than in DBA/2 mice. TNFalpha appears to mediate the production of chemokines responsible for neutrophil recruitment in the lungs. However, treatment of susceptible mice with TNFalpha led to an increase of neutrophil recruitment without any improvement in bacterial clearance. Lung homogenates from resistant mice also showed an increase in IL-10 and GM-CSF content. This was not seen in susceptible mice. This may lead to a more efficient neutrophil activation due to their effect on bacterial exotoxins and apoptotic gene regulation (via Fas pathway). TNFalpha, IL-10 and GM-CSF may represent valuable targets for treatment of lung infection with PA in patients unresponsive to antibiotherapy.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29892 |
| Date | January 1999 |
| Creators | Francoeur, Caroline. |
| Contributors | Gervais, Francine (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | French |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001681975, proquestno: MQ55058, Theses scanned by UMI/ProQuest. |
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