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Visualization of Dendritic cell IL-12 production and engagement with antigen-specific T cells during Mycobacterium tuberculosis infection in vivo

Objective

Mycobacterium tuberculosis (Mtb) is a major pathogen that continues to trouble mankind and puzzle immunologists. There is today a growing need for a better understanding of Mtb infection. Dendritic cells (DC) are unique in that they both prime T cells and through IL-12 production direct their differentiation into anti-mycobacterial effector cells. So studying DC and IL-12 during infection has direct implications for improving our fundamental grasp of immunity to this pathogen. DC-T cell contacts occur in the lymph node (LN). However, if and where DC produce IL-12 in vivo remains unknown. In fact, most of the data on DC responses to Mtb comes from in vitro studies that fail to consider the microenvironment of the LN and its constraints on cell-cell and cell-pathogen interactions. The questions herein address the spatiotemporal regulation of mycobacterial antigen acquisition and IL-12 production by DC and whether they give rise to antigen-specific interactions with T cells that dictate effector function generation. These questions remain at large due to methodological impediments. Visualization techniques provide a valuable insight into the complex in situ interplay between DC, Mtb and T cells that governs the host-pathogen standoff. Improvements in imaging now permit the undertaking of these studies in full dynamic view. Visualizing these vital interactions offer new perspectives into understanding and thus manipulating DC for immunotherapy and vaccination benefits.

Field of science

  • /medical and health sciences/basic medicine/immunology/immunotherapy
  • /medical and health sciences/clinical medicine/pneumology/tuberculosis

Call for proposal

FP7-PEOPLE-2009-RG
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Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Markus Maeurer (Prof.)