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

Antonio Bru, Pere Joan Cardona

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

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. © 2010 Bru, Cardona.
Original languageEnglish
Article numbere12985
JournalPLoS ONE
Volume5
Issue number9
DOIs
Publication statusPublished - 1 Nov 2010

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