Inflammatory signaling in human tuberculosis granulomas is spatially organized

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Inflammatory signaling in human tuberculosis granulomas is spatially organized. / 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.

In: Nature Medicine, Vol. 22, No. 5, 05.2016, p. 531-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Marakalala, MJ, Raju, RM, Sharma, K, Zhang, YJ, Eugenin, EA, Prideaux, B, Daudelin, IB, Chen, P-Y, Booty, MG, Kim, JH, Eum, SY, Via, LE, Behar, SM, Barry, CE, Mann, M, Dartois, V & Rubin, EJ 2016, 'Inflammatory signaling in human tuberculosis granulomas is spatially organized', Nature Medicine, vol. 22, no. 5, pp. 531-8. https://doi.org/10.1038/nm.4073

APA

Marakalala, M. J., Raju, R. M., Sharma, K., Zhang, Y. J., Eugenin, E. A., Prideaux, B., Daudelin, I. B., Chen, P-Y., Booty, M. G., Kim, J. H., Eum, S. Y., Via, L. E., Behar, S. M., Barry, C. E., Mann, M., Dartois, V., & Rubin, E. J. (2016). Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nature Medicine, 22(5), 531-8. https://doi.org/10.1038/nm.4073

Vancouver

Marakalala MJ, Raju RM, Sharma K, Zhang YJ, Eugenin EA, Prideaux B et al. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nature Medicine. 2016 May;22(5):531-8. https://doi.org/10.1038/nm.4073

Author

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. / Inflammatory signaling in human tuberculosis granulomas is spatially organized. In: Nature Medicine. 2016 ; Vol. 22, No. 5. pp. 531-8.

Bibtex

@article{0f827034ffc743b9839c2a1284fb691a,
title = "Inflammatory signaling in human tuberculosis granulomas is spatially organized",
abstract = "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.",
keywords = "Animals, Arachidonic Acid, Eicosanoids, Granuloma, Humans, Immunohistochemistry, Inflammation, Laser Capture Microdissection, Mass Spectrometry, Microscopy, Confocal, Proteomics, Rabbits, Reactive Oxygen Species, Signal Transduction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tuberculosis, Pulmonary, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural, Research Support, N.I.H., Extramural",
author = "Marakalala, {Mohlopheni J} and Raju, {Ravikiran M} and Kirti Sharma and Zhang, {Yanjia J} and Eugenin, {Eliseo A} and Brendan Prideaux and Daudelin, {Isaac B} and Pei-Yu Chen and Booty, {Matthew G} and Kim, {Jin Hee} and Eum, {Seok Yong} and Via, {Laura E} and Behar, {Samuel M} and Barry, {Clifton E} and Matthias Mann and V{\'e}ronique Dartois and Rubin, {Eric J}",
year = "2016",
month = may,
doi = "10.1038/nm.4073",
language = "English",
volume = "22",
pages = "531--8",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "nature publishing group",
number = "5",

}

RIS

TY - JOUR

T1 - Inflammatory signaling in human tuberculosis granulomas is spatially organized

AU - Marakalala, Mohlopheni J

AU - Raju, Ravikiran M

AU - Sharma, Kirti

AU - Zhang, Yanjia J

AU - Eugenin, Eliseo A

AU - Prideaux, Brendan

AU - Daudelin, Isaac B

AU - Chen, Pei-Yu

AU - Booty, Matthew G

AU - Kim, Jin Hee

AU - Eum, Seok Yong

AU - Via, Laura E

AU - Behar, Samuel M

AU - Barry, Clifton E

AU - Mann, Matthias

AU - Dartois, Véronique

AU - Rubin, Eric J

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

KW - Animals

KW - Arachidonic Acid

KW - Eicosanoids

KW - Granuloma

KW - Humans

KW - Immunohistochemistry

KW - Inflammation

KW - Laser Capture Microdissection

KW - Mass Spectrometry

KW - Microscopy, Confocal

KW - Proteomics

KW - Rabbits

KW - Reactive Oxygen Species

KW - Signal Transduction

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Tuberculosis, Pulmonary

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, N.I.H., Intramural

KW - Research Support, N.I.H., Extramural

U2 - 10.1038/nm.4073

DO - 10.1038/nm.4073

M3 - Journal article

C2 - 27043495

VL - 22

SP - 531

EP - 538

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 5

ER -

ID: 186877205