title: Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis.
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.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany. dorhoi@mpiib-berlin.mpg.de.
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany. kaufmann@mpiib-berlin.mpg.de.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009336:Necrosis; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*
keywords: Cavitation; Granuloma; Inflammation; Lung; Mycobacterium tuberculosis