Lcukocyte Ig-like receptors (LILR) are a family of innate immune receptors whose members have been shown 10 recognise both self and bacterial ligands. They can exert powerful immunomodulatory effects on monocytic cells and by doing so influence the adaptive immune response. Monocytic cells arc a target for mycobacterial infection, and LILR expression patterns correspond to leprosy disease phenotype during M.leprae infection. This thesis was based on the hypothesis that LJLR activity may also be relevant in tuberculosis. The main aim was to investigate LlLR with respect to infection with Mycobacterium bovis and to compare this with Mycobacterium tuberculosis infection. By measuring the transcription of LILR using qPCR, receptor expression was shown to be altered following culture of monocytic cells with mycobacteria. Culture with M bovis demonstrated the broadest change to expression patterns, with four L1LR down-regulated (LlLRA2, LILRA3, LlLRA6, LILRB 1), and one receptor, L1LRBS, up-regulated. In the absence of any previous published studies regarding the expression, ligand or potential functions of LlLRB5, further analyses were performed for this receptor L1LRBS transfectants exhibited signalling in the presence of BCG, indicating a relevance to mycobacterial recognition. Flow cytometric analysis demonstrated LILRBS expression on low numbers of mDC but on high numbers of T cells. Furthermore, crosslinking LI LRB5 revealed the down-regulation of CD80 on antigen presenting cells, which may impact on T cell activation. Phenotypic alterations were also detected on T cells following LILRBS crosslinking. Finally, cattle, as the natural hosts of M. bovis, were hypothesised to encode and express LILR. Here the identification and classification of 16 novel bovine L1LR was described. Cattle appear to have retained both LILR and Paired Ig-Like Receptors (pm.), which are thought to have evolved from a common ancestral gene, and whilst the signalling domains are more restricted than their human counterparts, cattle possess six genomically encoded soluble receptors.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:603593 |
| Date | January 2013 |
| Creators | Hogan, Louise |
| Publisher | St George's, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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