The role of the innate immune response (activation of dendritic cells and γ/δ T cells) in aberrant immune reactions during acute viral infections of infants
Project management at the University of Würzburg:
Activation of the innate immunity is essential for both the initial control of pathogens and the induction and quality of the adaptive immune response. Particularly for the control of bacterial infections, the contribution of components of the innate immune system, such as γ/δ T cells and professional antigen presenting cells (APC) (including macrophages and dendritic cells, DC) is well established. Activated γ/δ T cells develop cytotoxic activity which contributes to the elimination of infected cells, but is also involved in terminating the adaptive immune response. Mediators released from γ/δ T cells are essentially involved in recruitment and activation of α/β T cells, but also for components of the innate immune system including APC. These are located in peripheral tissues where they phagocyte and process, and after homing to secondary lymphatic tissues, present antigens via MHC molecules to T cells. Due to their unique ability to activate naive T cells, DC are essential for the induction of primary immune responses. Professional APC express Toll-like receptors (TLR) which, after engagement with bacterial cell wall components, trigger the induction of proinflammatory cytokines or monokines. The interference of pathogens with APC maturation, recruitment and function is a powerful strategy for immune evasion and thereby contributes to pathogenesis and the establishment of persistent infections. There is ample evidence that viruses causing acute diseases in infants such as particularly measles virus (MV) are effective in initiating virusspecific immune responses, but also lead to a suppression of particularly T cell responses to opportunistic pathogens. Whether and how these viruses modulate activation of the innate immune responses, particularly γ/δ T cells and APC, is unknown as yet. The recent finding that also a viral surface protein triggers APC activation by interacting with a member of the TLR family suggests that other viruses might use this strategy too. Based on these considerations, this project aims to investigate the interactions of viruses causing acute diseases in infants with components of the innate immune system directly in serial probes in clinical material. Based on the long standing experience of the grant applicants and the clinical importance of aberrant immune responses induced by this particular virus, our initial focus will be to study the modulation of APC and γ/δ T cell responses by MV. We also intend, however, to extend these studies to other viruses causing acute infection in children such as mumps, rubella, varicella and enterovirus. The study aims to contribute to a better understanding of how these viruses initiate protective immune responses, but also lead to the induction of aberrant immune responses to opportunistic infections in children.
Projekt period: from 05.2002 to 04.2004
Landeshaushalt Wissenschaftsministerium ,Granting date: 28.03.2002