MBI Publications

MBI Publications for Larry Schlesinger (6)

  • S. Dai, H. Curry, R. Leander and L. Schlesinger
    Fine tuning inflammation at the front door: Macrophage Complement Receptor 3-mediates phagocytosis and immune suppression for Francisella tularensis
    PLoS Pathog (Under Revision)

    Abstract

  • J. Day, A. Friedman and L. Schlesinger
    Modeling the immune rheostat of macrophages in the lung in response to infection
    Proc. Natl Acad Sci USAVol. 106 No. 27 (2009) pp. 11246-11251

    Abstract

    In the lung, alternatively activated macrophages (AAM) form the first line of defense against microbial infection. Due to the highly regulated nature of AAM, the lung can be considered as an immunosuppressive organ for respiratory pathogens. However, as infection progresses in the lung, another population of macrophages, known as classically activated macrophages (CAM) enters; these cells are typically activated by IFN-. CAM are far more
    effective than AAM in clearing the microbial load, producing proinflammatory cytokines and antimicrobial defense mechanisms necessary to mount an adequate immune response. Here, we are concerned with determining the first time when the population of CAM becomes more dominant than the population of AAM. This proposed €˜€˜switching time€™€™ is explored in the context of Mycobacterium tuberculosis (MTb) infection. We have developed a mathematical model that describes the interactions among cells, bacteria, and cytokines involved in the activation of both AAM and CAM. The model, based on a system of differential equations, represents a useful tool to analyze strategies for reducing the switching time, and to generate hypotheses for experimental testing.
  • J. Day, L. Schlesinger and A. Friedman
    Tuberculosis research: Going forward with a powerful "Translation Systems Biology" approach
    Tuberculosis (Edinb)Vol. 90 No. 1 (2010) pp. 7-8

    Abstract

    Due to the complexity of the immune response to a Mycobacterium tuberculosis infection, identifying new, effective therapies and vaccines to combat it has been a problematic issue. Although many advances have been made in understanding particular mechanisms involved, they have, to date, proved insufficient to provide real breakthroughs in this area of tuberculosis research. The term €œTranslational Systems Biology€? has been formally proposed to describe the use of experimental findings combined with mathematical modeling and/or engineering principles to understand complex biological processes in an integrative fashion for the purpose of enhancing clinical practice. This opinion piece discusses the importance of using a translational systems biology approach for tuberculosis research as a means by which to go forward with the potential for significant breakthroughs to occur.
  • J. Day, A. Friedman and L. Schlesinger
    Modeling the host response to inhalation anthrax
    J Theor BiolVol. 276 No. 1 (2011) pp. 199-208

    Abstract

    Inhalation anthrax, an often fatal infection, is initiated by endospores of the bacterium Bacillus anthracis, which are introduced into the lung. To better understand the pathogenesis of an inhalation anthrax infection, we propose a two-compartment mathematical model that takes into account the documented early events of such an infection. Anthrax spores, once inhaled, are readily taken up by alveolar phagocytes, which then migrate rather quickly out of the lung and into the thoracic/mediastinal lymph nodes. En route, these spores germinate to become vegetative bacteria. In the lymph nodes, the bacteria kill the host cells and are released into the extracellular environment where they can be disseminated into the blood stream and grow to a very high level, often resulting in the death of the infected person. Using this framework as the basis of our model, we explore the probability of survival of an infected individual. This is dependent on several factors, such as the rate of migration and germination events and treatment with antibiotics.
  • J. Day, A. Friedman and L. Schlesinger
    Modeling the immune rheostat of macrophages in the lung in response to infection.
    Proc. Natl Acad Sci USAVol. 106 No. 27 (2012) pp. 11246-11251

    Abstract

  • R. Leander, S. Dai, L. Schlesinger and A. Friedman
    A Mathematical Model of CR3/TLR2 Crosstalk in the context of Francisella Tularensis infection
    PLoS Comput Biol (2012) (Under Revision)

    Abstract

View Publications By