Type-I interferons (IFN-I) play a key protective role during viral infections, however, their role during bacterial infections remains unclear. We evaluated the influence of IFN-I signalling during infection of mice with the facultative intracellular bacterium, Salmonella typhimurium (ST). Wild-type (WT) C57BL/6J mice succumbed to infection by day 7 and death was accelerated in mice deficient in key innate immune mediators (IFN-gamma, TNF-alpha, iNOS-2). Surprisingly, IFN-I receptor-deficient (IFN-I R-/-) mice survived ST infection up to 35 days. Despite enhanced inflammation, WT mice displayed uncontrolled ST burden and lower macrophage numbers in the spleen, compared with IFN-I R-/- mice. In vitro, IFN-I-deficient macrophages expressed reduced levels of TNF-alpha and NO2- in response to ST and displayed prolonged survival in comparison with WT macrophages. Since macrophages play key protective roles during intracellular bacterial infections, our results indicate that IFN-I signalling during ST infection promotes the elimination of macrophages resulting in poor pathogen control.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/28658 |
| Date | January 2010 |
| Creators | Mulligan, Rebecca |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 116 p. |
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