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UK funding (£442,477): Effect of Cryptosporidium parvum infection of intestinal epithelial cells on mucosal NK cell function Ukri1 Jun 2008 UK Research and Innovation, United Kingdom
Overview
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Effect of Cryptosporidium parvum infection of intestinal epithelial cells on mucosal NK cell function
| Abstract | Cryptosporidiosis is an important diarrhoeal disease of humans and neonatal animals, including livestock, caused by a parasite Cryptosporidium that invades cells lining the intestine. The infection is eliminated by T cells of the immune system which produce interferon-gamma, a protein that activates other cells, including infected cells, to kill Cryptosporidium. Another cell that produces interferon-gamma in sufficient quantities to kill microbes is the natural killer (NK) cell. Hosts that have poor T cell function, such as neonates or AIDS patients, may develop severe infection with Cryptosporidium and die. We studied this problem using a mutant mouse that, like the AIDS patient, is T cell-deficient but have NK cells. We found that the mutant mouse develops a chronic infection similar to that often observed in AIDS patients and is often fatal. Initially the mouse controls infection by producing interferon-gamma but, later, this production ceases and the mouse loses the ability to curb parasite multiplication. This suggests that early in infection NK cells provide partial but potent immunity but later the chronic infection causes NK cells either to disappear or malfunction. In this investigation, we will investigate in detail the role of NK cells in the control of chronic C. parvum infection in T cell deficient mice. Use will be made of different mutant strains of mice that have no T cells and either possess or do not possess NK cells. By comparing infection levels in these strains of mice it will be established whether NK cells are required for control of infection. NK cells will be isolated during infection to determine whether they are the source of interferon gamma. NK cells were originally named because of their capacity to directly kill tumour cells while in direct contact and we will determine whether they can also kill cells infected with C. parvum. The cells infected by C. parvum produce molecules that are known to activate NK cells and we will investigate whether NK cells isolated from the intestine and other organs can be activated in the presence of infected cells to produce interferon -gamma. Finally, to find out why mice eventually succumb to infection, intestinal cells will be isolated from mice at early and late stages of chronic infection and comparisons made of NK cell numbers and functionality. This study may lead to new therapies that allow NK cells to survive and maintain production of interferon-gamma during chronic infections. |
| Category | Research Grant |
| Reference | BB/F006179/1 |
| Status | Closed |
| Funded period start | 01/06/2008 |
| Funded period end | 31/05/2011 |
| Funded value | £442,477.00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FF006179%2F1 |
Participating Organisations
| Queen Mary University of London |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: Queen Mary University of London, London.
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