Linked Life Data

19265149

Source:http://linkedlifedata.com/resource/pubmed/id/19265149

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-3-6
pubmed:abstractText
Mycobacterium tuberculosis is one of the world's most deadly human pathogens; an integrated understanding of how it successfully survives in its host is crucial to developing new treatment strategies. One notable characteristic of infection with M. tuberculosis is the formation of granulomas, aggregates of immune cells whose structure and function may reflect success or failure of the host to contain infection. One central regulator of host responses to infection, including granuloma formation, is the pleiotropic cytokine TNF-alpha. Experimental work has characterized roles for TNF in macrophage activation; regulation of apoptosis; chemokine and cytokine production; and regulation of cellular recruitment via transendothelial migration. Separating the effects of these functions is presently difficult or impossible in vivo. To this end, we applied a computational model to understand specific roles of TNF in control of tuberculosis in a single granuloma. In the model, cells are represented as discrete entities on a spatial grid responding to environmental stimuli by following programmed rules determined from published experimental studies. Simulated granulomas emerge as a result of these rules. After confirming the importance of TNF in this model, we assessed the effects of individual TNF functions. The model predicts that multiple TNF activities contribute to control of infection within the granuloma, with macrophage activation as a key effector mechanism for controlling bacterial growth. Results suggest that bacterial numbers are a strong contributing factor to granuloma structure with TNF. Finally, TNF-dependent apoptosis may reduce inflammation at the cost of impairing mycobacterial clearance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3706-17
pubmed:dateRevised
2011-9-30
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Synergy between individual TNF-dependent functions determines granuloma performance for controlling Mycobacterium tuberculosis infection.
pubmed:affiliation
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural