Use this URL to cite or link to this record in EThOS:
Title: Characterization of human Natural Killer cell response to Aspergillus fumigatus
Author: Pinto, Virginia Manuela Santiago
ISNI:       0000 0004 6061 707X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Invasive aspergillosis is a major cause of morbidity and mortality in acute myeloid leukaemia (AML) (1-3) and Aspergillus fumigatus has been identified as the most common species causing invasive disease in these patients (2,4). The adoptive transfer of natural killer (NK) cells has been described as a promising therapeutic tool for AML (5,6) and it has been suggested as an attractive strategy in the prophylaxis of common infections in these patients. This PhD aimed to characterize the human NK cell response to A. fumigatus in order to assess the potential use of these cells to prevent this fungal infection. The interaction between NK cells and A. fumigatus in vitro resulted in cell adherence to the fungus, polarization of the lytic granules towards A. fumigatus, NK cell degranulation and chemokine release. The co-culture of NK cells and A. fumigatus also resulted in CD56 downregulation on NK cell surface, a process that might represent a novel mechanism of immune evasion for A. fumigatus. The analysis of NK cell antifungal activity demonstrated that NK cells do not contain fungal growth, however the cells have shown to induce fungal DNA release that has been associated to fungal damage (7,8) and might mediate immune cell activation since pathogen-derived DNA has been shown to stimulate the widely expressed TLR9 receptor (9-11). AML-derived NK cells were shown to maintain their ability to polarize the lytic granules towards A. fumigatus and to induce fungal DNA release. In conclusion, my findings suggest that the role of NK cells in the immune response against A. fumigatus infection might be indirect, through the recruitment of immune cells to the site of infection and the induction of immune cell activation mediated by fungal DNA. Therefore, my results suggest that the infusion of NK cells on their own would be insufficient to control A. fumigatus infection in AML patients.
Supervisor: Armstrong-James, Darius ; Kelleher, William P. ; Rezvani, Katy Sponsor: Fundacao para a Ciencia e a Tecnologia
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral