A Systems Biologist's View of Dendritic Cell–Cytotoxic T Lymphocyte Interaction

Ludewig, Burkhard; Bocharov, Gennady

doi:10.1002/9783527619696.ch23

Cited by 2 publications

(2 citation statements)

References 156 publications

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“…To describe quantitatively the structure, dynamics and the operating principles that permit pDCs to initially shield the host against an overwhelming spread of the cytopathic MHV infection, we followed a systems biology approach as outlined previously [11] , [12] . First, we decomposed the system dynamics into a set of ‘elementary’, well-documented processes such as the virus replication, target cell turnover and IFN-α decay, as well as the production of virus and IFN-α by infected cells ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

et al. 2010

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Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 103 to 104 Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.

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Section: Resultsmentioning

confidence: 99%

A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

et al. 2010

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“…In the case of the interaction between dendritic cells (DCs) and cytotoxic T lymphocytes (CTL), which is central for immune defense, modules can be specified at various levels: the thymus acting as 'educational' module, the secondary lymphoid organs functioning as 'activation' module and the peripheral organs as 'surveillance' module. An extensive discussion of the priming of functional CTL responses with DCs following the systems approach is presented in [74].…”

Section: Modulesmentioning

confidence: 99%

Understanding Complex Regulatory Systems: Integrating Molecular Biology and Systems Analysis

Bocharov¹

2005

Transfus Med Hemother

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In this article, the application of systems analysis to complex regulatory phenomena in biology was reviewed. It is regarded as an emerging interdisciplinary field of systems biology based on the extensive use of a range of mathematical modeling tools allowing the integration of various regulation levels - from the molecular level to the level of the entire system. Understanding the complex biological systems relies upon the analysis of structure, design, methods of control/coordination and dynamics. The methodology of analysis is presented by considering examples from cellular signaling networks and the immune response regulation. The concepts of feedback and feedforward regulation, modularity and redundancy, which are central for the robust performance of biological systems, are discussed. Some typical structural and regulatory patterns in molecular networks underlying certain types of response behavior (e.g. biphasic response) are described, and the foundations of the computational modeling of complex biological processes grounded in the mathematical systems theory and information-theoretic approaches are outlined. We present a case study on the robustness of the dendritic cell (DC)-based cytotoxic Tlymphocyte (CTL) priming aimed at identifying the control parameters, which relies upon mathematical modeling in conjunction with experimental examination.

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A Systems Biologist's View of Dendritic Cell–Cytotoxic T Lymphocyte Interaction

Cited by 2 publications

References 156 publications

A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

Understanding Complex Regulatory Systems: Integrating Molecular Biology and Systems Analysis

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