title: Mathematical Model of Oxygen Transport in Tuberculosis Granulomas.
abstract: Pulmonary granulomas--the hallmark of Mycobacterium tuberculosis (MTB) infection--are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis-Menten kinetics. An approximate analytical solution--using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis--was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.
authors.affiliation: Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Cox 7, 100 Blossom Street, Boston, MA, 02114, USA.|Department of Chemical and Biological Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Meenal
authors.initials: M
authors.lastname: Datta
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892, USA.|Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.affiliation: Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Cox 7, 100 Blossom Street, Boston, MA, 02114, USA.|Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Departments of Biomedical and Mechanical Engineering, Bucknell University, Lewisburg, PA, 17837, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Baish
authors.affiliation: Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Cox 7, 100 Blossom Street, Boston, MA, 02114, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892, USA.|Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.affiliation: Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Cox 7, 100 Blossom Street, Boston, MA, 02114, USA. jain@steele.mgh.harvard.edu.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006099:Granuloma / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000473:pathology; D008954:Models, Biological; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D015657:Respiratory Transport; D014397:Tuberculosis, Pulmonary / Q000378:metabolism* / Q000473:pathology
chemical_list: D010100:Oxygen
keywords: Diffusion; Michaelis–Menten kinetics; Mycobacterium tuberculosis; Pimonidazole; Rabbit model