Document Detail


Monocytes from tuberculosis patients that exhibit cleaved caspase 9 and denaturalized cytochrome-C are more susceptible to death mediated by TLR2.
MedLine Citation:
PMID:  22133266     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Experimental models have shown that lipoproteins from Mycobacterium tuberculosis (Mtb) induce apoptosis via TLR2 in the THP-1 cell line and in monocyte-derived macrophages from healthy volunteers. We found an increased percentage of circulating monocytes in tuberculosis (TB) patients in comparison to healthy controls. TB patients showed a higher TLR2 and TLR4 expression density on monocytes, and a higher proportion of TLR2(+) monocytes, as well as increased serum TNF-alpha level. In culture, monocytes from TB patients were more susceptible to undergo death than monocytes from healthy controls. Moreover, death susceptible monocytes were positive to both TLR2 and TLR4 at the start of culture. Freshly obtained monocytes from TB patients exhibited cleaved caspase 9 and denaturalized cytochrome-C. Regarding caspase 8, ASK1, and phospho-p38 MAPK levels, no difference was observed between samples from TB patients and healthy controls. The culture filtrate antigen extract (CFAE) from Mtb H37Rv strain induced TB patient-monocytes death after 4-h incubation, which was abrogated by neutralizing antibodies for TLR2 but not TLR4. Similarly, Pam3CSK4, a synthetic agonist triacylated ligand to TLR2 also induced death of monocytes, although it did not increase the cleaved caspase 9 level. Our findings suggest that monocytes from TB patients are more susceptible to die probably due to mitochondrial damage, and that cell death increases in the presence of mycobacterial antigen by a TLR2-dependent pathway.
Authors:
Leslie Chavez-Galán; Isabel Sada-Ovalle; Renata Baez-Saldaña; Raúl Chávez; Ricardo Lascurain
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-1
Journal Detail:
Title:  Immunology     Volume:  -     ISSN:  1365-2567     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal compilation © 2011 Blackwell Publishing Ltd.
Affiliation:
Laboratorio de Inmunología Integrativa Departamento de Bioquímica Clínica de Tuberculosis y Enfermedades Pleurales, Instituto Nacional de Enfermedades Respiratorias. Ismael Cosío Villegas, Calzada de Tlalpan 4502, 14080, Mexico. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, PO Box 70159, 04510, Mexico.
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