Abstract : Tuberculosis (TB) is one of the earliest recorded human diseases and still one of the deadliest wor
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Abstract : Tuberculosis (TB) is one of the earliest recorded human diseases and still one of the deadliest worldwide. Its causative agent is the bacteria Mycobacterium tuberculosis (Mtb). Cytokine-mediated macrophage activation is a necessary step in control of bacterial growth and early immunologic events in lymph node and lung are crucial to the outcome of infection although the factors that influence these environments and the immune response are poorly understood. Our goal is to build the next-generation two-compartmental model of the immune response to provide a gateway to more spatial and mechanistic investigations of M. tuberculosis infection in the LN and lung. Crucial immune factors emerge that affect macrophage populations and inflammation namely TNF-dependent recruitment and apoptosis and IL-10 levels. Surprisingly bacterial load plays a less important role than TNF in increasing the population of infected macrophages and inflammation. Using a mathematical model it is possible to distinguish the effects of pro-inflammatory (TNF) and anti-inflammatory (IL-10) cytokines on the spectrum of phagocyte populations (macrophages and dendritic cells) in the lung and lymph node. Our results suggest that TNF is a major mediator of recruitment of phagocytes to the lungs. In contrast IL-10 plays a role in balancing the dominant macrophage phenotype in LN and lung.Copyright (c) 2010 Elsevier Ltd. All rights reserved.PMID 20510249 PubMed - indexed for MEDLINEPublication Types MeSH Terms Substances Grant SupportPublication Types Research Support N.I.H. ExtramuralMeSH TermsAnimalsCell PolarityDendritic Cells/immunologyDendritic Cells/microbiologyHumansImmunomodulation/immunologyInterleukin-10/immunology*Lung/immunology*Lung/microbiologyLung/pathologyLymph Nodes/immunology*Lymph Nodes/microbiologyLymph Nodes/pathologyMacrophages/cytologyMacrophages/immunologyMacrophages/microbiologyMiceMice Inbred C57BLModels Immunological*Mycobacterium tuberculosis/immunologyPhagocytes/cytologyPhagocytes/immunology*Reproducibility of ResultsT-Lymphocytes/immunologyT-Lymphocytes/microbiologyTuberculosis/immunology*Tumor Necrosis Factor-alpha/immunology*SubstancesTumor Necrosis Factor-alphaInterleukin-10Grant SupportHL092853/HL/NHLBI NIH HHS/United StatesLM00902701/LM/NLM NIH HHS/United StatesN01 AI50018/AI/NIAID NIH HHS/United StatesR01HL71241/HL/NHLBI NIH HHS/United StatesLinkOut - more resourcesFull Text SourcesElsevier ScienceEBSCOSwets Information ServicesOther Literature SourcesCOS Scholar UniverseMedicalTuberculosis - MedlinePlus Health Information Supplemental Content Related citations Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol. 2007 Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo.Wolf AJ Linas B Trevejo-Nuñez GJ Kincaid E Tamura T Takatsu K Ernst JD. J Immunol. 2007 Aug 15 179(4)2509-19. Enhanced macrophage activity in granulomatous lesions of immune mice challenged with Mycobacterium tuberculosis. J Immunol. 2006 Enhanced macrophage activity in granulomatous lesions of immune mice challenged with Mycobacterium tuberculosis.Ordway D Harton M Henao-Tamayo M Montoya R Orme IM Gonzalez-Juarrero M. J Immunol. 2006 Apr 15 176(8)4931-9. The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection. J Theor Biol. 2008 The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection.Ray JC Wang J Chan J Kirschner DE. J Theor Biol. 2008 May 7 252(1)24-38. Epub 2008 Jan 20. 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UniGene UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records. GEO Profiles Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile. Recent activity Clear Turn Off Turn On TNF and IL-10 are major factors in modulation of the phagocytic cell environment... TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis a next-generation two-compartmental model.J Theor Biol. 2010 Aug 21 265(4)586-98. Epub 2010 May 25 . PubMed Your browsing activity is empty. Activity recording is turned off. Turn recording back on See more... 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