Modeling the immune rheostat of macrophages in the lung in response to infection.
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-gamma. 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.
Day
Judy
J
Mathematical Biosciences Institute, Ohio State University, Columbus, OH 43210, USA.
Friedman
Avner
A
Schlesinger
Larry S
LS
D003198:Computer Simulation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005110:Extracellular Space / Q000382:microbiology; D007107:Immune System / Q000276:immunology* / Q000382:microbiology*; D042541:Intracellular Space / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology*; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D013997:Time Factors
D016207:Cytokines