HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wigginton, J. E. Articles by Kirschner, D. Search for Related Content PubMed PubMed Citation Articles by Wigginton, J. E. Articles by Kirschner, D.

A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis¹

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

A key issue for the study of tuberculosis infection (TB) is to understand why individuals infected with Mycobacterium tuberculosis experience different clinical outcomes. Elaborating the immune mechanisms that determine whether an infected individual will suffer active TB or latent infection can aid in developing treatment and prevention strategies. To better understand the dynamics of M. tuberculosis infection and immunity, we have developed a virtual human model that qualitatively and quantitatively characterizes the cellular and cytokine control network operational during TB infection. Using this model, we identify key regulatory elements in the host response. In particular, factors affecting cell functions, such as macrophage activation and bactericidal capabilities, and effector T cell functions such as cytotoxicity and cytokine production can each be determinative. The model indicates, however, that even if latency is achieved, it may come at the expense of tissue damage if the response is not properly regulated. A balance in Th1 and Th2 immune responses governed by IFN-, IL-10, and IL-4 facilitate this down-regulation. These results are further explored through virtual deletion and depletion experiments.

This article has been cited by other articles:

				J. Day, A. Friedman, and L. S. Schlesinger Modeling the immune rheostat of macrophages in the lung in response to infection PNAS, July 7, 2009; 106(27): 11246 - 11251. [Abstract] [Full Text] [PDF]

				R. R. Ganta, C. Cheng, E. C. Miller, B. L. McGuire, L. Peddireddi, K. R. Sirigireddy, and S. K. Chapes Differential Clearance and Immune Responses to Tick Cell-Derived versus Macrophage Culture-Derived Ehrlichia chaffeensis in Mice Infect. Immun., January 1, 2007; 75(1): 135 - 145. [Abstract] [Full Text] [PDF]

				J. Detilleux, F. Vangroenweghe, and C. Burvenich Mathematical Model of the Acute Inflammatory Response to Escherichia coli in Intramammary Challenge. J Dairy Sci, September 1, 2006; 89(9): 3455 - 3465. [Abstract] [Full Text] [PDF]

				A. F.M Maree, R. Kublik, D. T Finegood, and L. Edelstein-Keshet Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease? Phil Trans R Soc A, May 15, 2006; 364(1842): 1267 - 1282. [Abstract] [Full Text] [PDF]

				D. Sud, C. Bigbee, J. L. Flynn, and D. E. Kirschner Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection J. Immunol., April 1, 2006; 176(7): 4296 - 4314. [Abstract] [Full Text] [PDF]

				S. Marino, S. Pawar, C. L. Fuller, T. A. Reinhart, J. L. Flynn, and D. E. Kirschner Dendritic Cell Trafficking and Antigen Presentation in the Human Immune Response to Mycobacterium tuberculosis J. Immunol., July 1, 2004; 173(1): 494 - 506. [Abstract] [Full Text] [PDF]

				D. J. Weiss, O. A. Evanson, A. Moritz, M. Q. Deng, and M. S. Abrahamsen Differential Responses of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium Infect. Immun., October 1, 2002; 70(10): 5556 - 5561. [Abstract] [Full Text] [PDF]