MicroRNAs (miRNAs) function through targeted binding to the 3’ un-translated region (UTR) of messenger RNAs (mRNAs) in a sequence specific manner. Recent studies have implicated microRNA-155 (miR-155) as an important player in the development and function of a number of immune cells including B and T cells, macrophages and dendritic cells. The aim of this study was to investigate the role of miR-155 in controlling either a mucosal <i>Citrobacter rodentium </i>or a systemic <i>Salmonella enterica </i>serovar Typhimurium infection in the context of the overall immune response. Here we present evidence that miR-155-deficient mice are less competent in their ability to eradicate a mucosal <i>C. rodentium </i>infection compared with wild type control C57BL/6 mice. We show that miR-155-deficient mice have a higher <i>C. rodentium </i>burden in gastrointestinal tissue and also exhibit spread into systemic tissues. Additionally, we demonstrate that germinal centre formation and humoral immune responses are impaired in the absence of miR-155. In view of the fact that this phenotype is largely reproduced in μMT (B cell-deficient) mice reconstituted with miR-155-deficient B cells we conclude that miR-155 is required to control <i>C. rodentium </i>infection. Further, miR-155-deficient mice were able to clear a primary infection with an attenuated strain of <i>S. Typhimurium </i>but were defective in their immune response to <i>Salmonella.</i>
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:605614 |
| Date | January 2011 |
| Creators | John, V. F. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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