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...

Full description

Saved in:
Bibliographic Details
Published in:Nature medicine Vol. 22; no. 5; pp. 531 - 538
Main Authors: 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
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.05.2016
Nature Publishing Group
Subjects:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography: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