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Seminars in Immunopathology
Published in: Seminars in Immunopathology 2/2016

01-03-2016 | Review

Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis

Authors: Anca Dorhoi, Stefan H.E. Kaufmann

Published in: Seminars in Immunopathology | Issue 2/2016

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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 interferons (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.
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Metadata
Title
Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis
Authors
Anca Dorhoi
Stefan H.E. Kaufmann
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 2/2016
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-015-0531-3

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