Inflammatory signaling in human tuberculosis granulomas is spatially organized

Using proteomic analyses, Eric Rubin, Véronique Dartois and colleagues show that tuberculosis granulomas have spatially segregated protein compositions that compartmentalize pro- and anti-inflammatory responses to distinct regions. Granulomas are the pathological hallmark of tuberculosis (TB). Howev...

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Vydáno v:	Nature medicine Ročník 22; číslo 5; s. 531 - 538
Hlavní autoři:	Marakalala, Mohlopheni J, Raju, Ravikiran M, Sharma, Kirti, Zhang, Yanjia J, Eugenin, Eliseo A, Prideaux, Brendan, Daudelin, Isaac B, Chen, Pei-Yu, Booty, Matthew G, Kim, Jin Hee, Eum, Seok Yong, Via, Laura E, Behar, Samuel M, Barry, Clifton E, Mann, Matthias, Dartois, Véronique, Rubin, Eric J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.05.2016 Nature Publishing Group
Témata:	13/51 14/19 14/63 631/1647/2067 631/1647/664/1257 631/1647/767/1424 692/699/255/1856 82/80 Animals Arachidonic Acid - metabolism Biomedicine Cancer Research Cellular signal transduction Development and progression Eicosanoids - immunology Eicosanoids - metabolism Genetic aspects Granuloma Granuloma - immunology Granuloma - metabolism Granuloma - pathology Health aspects Humans Immunohistochemistry Infectious Diseases Inflammation Inflammation - immunology Inflammation - metabolism Inflammation - pathology Laser Capture Microdissection Lesions Mass Spectrometry Metabolic Diseases Microscopy Microscopy, Confocal Molecular Medicine Mycobacterium Neurosciences Pathology Peptides Properties Proteomics Rabbits Reactive Oxygen Species - immunology Reactive Oxygen Species - metabolism Signal Transduction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tuberculosis Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - metabolism Tuberculosis, Pulmonary - pathology Tumor proteins
ISSN:	1078-8956, 1546-170X, 1546-170X
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Shrnutí:	Using proteomic analyses, Eric Rubin, Véronique Dartois and colleagues show that tuberculosis granulomas have spatially segregated protein compositions that compartmentalize pro- and anti-inflammatory responses to distinct regions. Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner. Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas. We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature. These findings are consistent across a set of six human subjects and in rabbits. Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma. From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.
Bibliografie:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 these authors contributed equally; arranged alphabetically
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/nm.4073