Award details

BBSRC-funded studentship: Interactions of dendritic cells, natural killer cells and chemokines in M bovis infection

Reference	BBS/E/I/00001347
Principal Investigator / Supervisor	Professor Jayne Hope
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	11,200
Status	Completed
Type	Institute Project
Start date	01/10/2007
End date	30/09/2011
Duration	48 months

Abstract

Dendritic cells (DC) are the most important antigen-presenting cells involved in early immune responses and are considered to form a 'bridge' linking innate and adaptive immune responses being able to directly trigger innate cell functions as well as primary cognate responses in immunologically naive animals. The interaction of DC with natural killer (NK) cells may be pivotal in determining early immune bias through rapid secretion of IFN-gamma and cytolytic activity against infected cells. Infection of DC with the pathogen Mycobacterium bovis induces secretion of cytokines such as IL-12 and IL-18, and upregulation of molecules such as CD40, that are known to be involved in NK cell stimulation. Stimulation of IFN-gamma secretion by NK cells by M. bovis infected DC may contribute to protective Th1 biased immune responses central to disease resolution. Despite in vitro evidence for DC-NK interaction, the tissue location in which DC and NK cells interact and the signals involved in bringing these cells together in vivo are poorly understood. Cell migration is controlled by complex interactions between chemokines and their receptors. This project will test the hypothesis that infection of DC induces chemokine secretion that induces the migration of NK cells from blood into lymph nodes where DC-NK interactions can proceed. The in vivo colocalisation of DC and NK cells in normal and antigenically challenged lymph nodes will be assessed. In vitro the ability of DC to influence chemotaxis of NK cells, and the effects of M. bovis infection on the ability of DC to chemoattract NK cells will be assessed. Assessment of the expression of chemokine receptors on NK cells will focus on CXCR3 and CCR5 initially as these have defined roles in DC-NK interactions in human and/or mouse. Overall, understanding the interaction of DC and NK cells following infection with M. bovis could allow targeted immune intervention strategies for improved immune responses.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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