The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
The 19-kDa Mycobacterium tuberculosis Protein Induces Macrophage Apoptosis Through Toll-Like Receptor-2
Abstract
Macrophages infected with Mycobacterium tuberculosis undergo increased rates of apoptosis. Important objectives are to define the microbial factors that cause apoptosis, the mechanisms involved and the impact on infection. The 19-kDa M. tuberculosis glycolipoprotein (p19) is both cell wall-associated and secreted and is a candidate virulence factor. We investigated the potential of recombinant, His-tagged p19 lacking the secretion/acylation signal to induce macrophage apoptosis. The TUNEL assay and annexin V binding to membrane phosphatidylserine were used to measure apoptosis. The results show that p19 does act to induce apoptosis in differentiated THP-1 cells and monocyte-derived macrophages and that this effect is both dose- and time-dependent. Furthermore, this effect of p19 is Toll-like receptor (TLR)-2-mediated because preincubation of either THP-1 cells or TLR-2-expressing CHO cells with anti-TLR-2 mAb inhibited apoptosis induced by p19. Apoptosis of macrophages in response to p19 was found to be caspase-8 dependent and caspase-9 independent consistent with a transmembrane pathway signaling cell death through TLR-2. The viability of M. tuberculosis in cells undergoing apoptosis induced by p19 was significantly reduced suggesting the possibility that this may favor containment of infection. Although native p19 is a mycobacterial glycolipoprotein, based upon the use of recombinant p19 where the acylation signal had been removed, we conclude that it is the polypeptide component of p19 that is responsible for signaling through TLR-2 and that the lipid moiety is not required.
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Cites
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
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Cited by
To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis
Kucharczak, J., Simmons, M. J., Fan, Y., & Gélinas, C. (2003) · Oncogene · doi:10.1038/sj.onc.1207230 · Cited by 769
Virulence factors of the Mycobacterium tuberculosis complex
Forrellad, M. A., Klepp, L. I., Gioffré, A., Sabio y García, J., Morbidoni, H. R., Santangelo, M. D. L. P., Cataldi, A. A., & Bigi, F. (2013) · Virulence · doi:10.4161/viru.22329 · Cited by 622
Favaloro, B., Allocati, N., Graziano, V., Di Ilio, C., & De Laurenzi, V. (2012) · Aging · doi:10.18632/aging.100459 · Cited by 585
Innate immunity in tuberculosis: host defense vs pathogen evasion
Liu, C. H., Liu, H., & Ge, B. (2017) · Cellular & Molecular Immunology · doi:10.1038/cmi.2017.88 · Cited by 532
Lipoproteins of Bacterial Pathogens
Kovacs-Simon, A., Titball, R. W., & Michell, S. L. (2011) · Infection and Immunity · doi:10.1128/iai.00682-10 · Cited by 440
Metadata
- Authors
- López, M., Sly, L. M., Luu, Y., Young, D., Cooper, H., & Reiner, N. E.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-03-01
- Volume
- 170
- Issue
- 5
- Pages
- 2409-2416
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1941961496
- Cited by
- 269
- References
- 45
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- closed
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- López, M., Sly, L. M., Luu, Y., Young, D., Cooper, H., & Reiner, N. E. (2003). The 19-kDa Mycobacterium tuberculosis Protein Induces Macrophage Apoptosis Through Toll-Like Receptor-2. The Journal of Immunology. https://doi.org/10.4049/jimmunol.170.5.2409
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