Content area
Full Text
Semin Immunopathol (2016) 38:153166 DOI 10.1007/s00281-015-0531-3
http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s00281-015-0531-3&domain=pdf
Web End = REVIEW
Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis
Anca Dorhoi1 & Stefan H.E. Kaufmann1
Received: 1 September 2015 /Accepted: 13 September 2015 /Published online: 5 October 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Heightened morbidity and mortality in pulmonary tuberculosis (TB) are consequences of complex disease processes triggered by the causative agent, Mycobacterium tuberculosis (Mtb). Mtb modulates inflammation at distinct stages of its intracellular life. Recognition and phagocytosis, replication in phagosomes and cytosol escape induce tightly regulated release of cytokines [including interleukin (IL)-1, tumor necrosis factor (TNF), IL-10], chemokines, lipid mediators, and type I inter-ferons (IFN-I). Mtb occupies various lung lesions at sites of pathology. Bacteria are barely detectable at foci of lipid pneumonia or in perivascular/bronchiolar cuffs. However, abundant organisms are evident in caseating granulomas and at the cavity wall. Such lesions follow polar trajectories towards fibrosis, encapsulation and mineralization or liquefaction, extensive matrix destruction, and tissue injury. The outcome is determined by immune factors acting in concert. Gradients of cytokines and chemokines (CCR2, CXCR2, CXCR3/CXCR5 agonists; TNF/ IL-10, IL-1/IFN-I), expression of activation/death markers on immune cells (TNF receptor 1, PD-1, IL-27 receptor) or abundance of enzymes [arginase-1, matrix metalloprotease (MMP)-1, MMP-8, MMP-9] drive genesis and progression of lesions. Distinct lesions coexist such that inflammation in TB encompasses a spectrum of tissue changes. A better understanding of the multidimensionality of immunopathology in TB will inform novel therapies against this pulmonary disease.
Keywords Mycobacterium tuberculosis . Lung . Granuloma . Cavitation . Inflammation
AbbreviationsAhr Aryl hydrocarbon receptorAMPK 5' AMP-activated protein kinasecGAS Cyclic GMP-AMP synthaseCR Complement receptorCT Computer tomographyDC-SIGN Dendritic cell-specific ICAM-grabbing nonintegrin DTH Delayed-type hypersensitivityFDG 18-fluoro-deoxy-glucoseGM-CSF Granulocytemacrophage colony-stimulating factorHIF Hypoxia-inducible factorIDO-1 Indoleamine 2,3-dioxygenase-1IFN InterferonIFNAR1 IFN-alpha receptor 1IL InterleukiniNOS Inducible nitric oxide synthaseLTBI Latent Mtb infectionManLAM Mannose-capped lipoarabinomannanMARCO Macrophage receptor with collagenous structure MCL Macrophage C-type lectinMDSC Myeloid-derived suppressor cellMINCLE Macrophage-inducible Ca2+-dependent (C-type) lectinMMP Matrix metalloproteaseMtb Mycobacterium tuberculosisNEC Necrosis-associated extracellular cluster NF-B Nuclear factor kappa-light-chain-enhancer of activated B cellsNHP Nonhuman primateNK Natural killer
This article is a contribution to the Special Issue on Immunopathology of Mycobacterial...