Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice

PLoS One. 2010 Sep 23;5(9):e12985. doi: 10.1371/journal.pone.0012985.

Abstract

Background: Mycobacterium tuberculosis is a particularly aggressive microorganism and the host's defense is based on the induction of cellular immunity, in which the creation of a granulomatous structure has an important role.

Methodology: We present here a new 2D cellular automata model based on the concept of a multifunctional process that includes key factors such as the chemokine attraction of the cells; the role of innate immunity triggered by natural killers; the presence of neutrophils; apoptosis and necrosis of infected macrophages; the removal of dead cells by macrophages, which induces the production of foamy macrophages (FMs); the life cycle of the bacilli as a determinant for the evolution of infected macrophages; and the immune response.

Results: The results obtained after the inclusion of two degrees of tolerance to the inflammatory response triggered by the infection shows that the model can cover a wide spectrum, ranging from highly-tolerant (i.e. mice) to poorly-tolerant hosts (i.e. mini-pigs or humans).

Conclusions: This model suggest that stopping bacillary growth at the onset of the infection might be difficult and the important role played by FMs in bacillary drainage in poorly-tolerant hosts together with apoptosis and innate lymphocytes. It also shows the poor ability of the cellular immunity to control the infection, provides a clear protective character to the granuloma, due its ability to attract a sufficient number of cells, and explains why an already infected host can be constantly reinfected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokines / immunology
  • Granuloma / immunology
  • Granuloma / microbiology
  • Host-Pathogen Interactions
  • Humans
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Models, Biological
  • Models, Theoretical
  • Mycobacterium tuberculosis / chemistry*
  • Mycobacterium tuberculosis / growth & development*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / physiology
  • Swine
  • Swine, Miniature
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology*

Substances

  • Chemokines