A multi-scale approach to designing therapeutics for tuberculosis.
Approximately one third of the world's population is infected with Mycobacterium tuberculosis. Limited information about how the immune system fights M. tuberculosis and what constitutes protection from the bacteria impact our ability to develop effective therapies for tuberculosis. We present an in vivo systems biology approach that integrates data from multiple model systems and over multiple length and time scales into a comprehensive multi-scale and multi-compartment view of the in vivo immune response to M. tuberculosis. We describe computational models that can be used to study (a) immunomodulation with the cytokines tumor necrosis factor and interleukin 10, (b) oral and inhaled antibiotics, and
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA. linderma@umich.edu.
Jennifer J
JJ
Linderman
Nicholas A
NA
Cilfone
Elsje
E
Pienaar
Chang
C
Gong
Denise E
DE
Kirschner
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D015415:Biomarkers; D019295:Computational Biology; D003198:Computer Simulation; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006099:Granuloma / Q000188:drug therapy; D006801:Humans; D007107:Immune System; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D009169:Mycobacterium tuberculosis; D011381:Programming Languages; D049490:Systems Biology; D014376:Tuberculosis / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016207:Cytokines; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10