The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Host Genotype-Specific Therapies Can Optimize the Inflammatory Response to Mycobacterial Infections
Open accessAbstract
Summary Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A4 hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B4. We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.
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The zebrafish reference genome sequence and its relationship to the human genome.
Howe, K., Clark, M. D., Torroja, C. F., Torrance, J., Berthelot, C., Muffato, M., Collins, J. E., Humphray, S., McLaren, K., Matthews, L., et al. (2013) · Nature · doi:10.1038/nature12111 · Cited by 5,100
Pro-resolving lipid mediators are leads for resolution physiology
Serhan, C. N. (2014) · Nature · doi:10.1038/nature13479 · Cited by 3,041
Self-citationPai, M., Behr, M. A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C. C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.76 · Cited by 1,270
Advances in the development of new tuberculosis drugs and treatment regimens
Zumla, A., Nahid, P., & Cole, S. T. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4001 · Cited by 893
Roca, F. J., & Ramakrishnan, L. (2013) · Cell · doi:10.1016/j.cell.2013.03.022 · Cited by 592
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Metadata
- Authors
- Tobin, D. M., Roca, F. J., Oh, S. F., McFarland, R., Vickery, T. W., Ray, J. P., Ko, D. C., Zou, Y., Bang, N. D., Chau, T. T. H., Vary, J. C., Hawn, T. R., Dunstan, S. J., Farrar, J. J., Thwaites, G. E., King, M.-C., Serhan, C. N., & Ramakrishnan, L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 148
- Issue
- 3
- Pages
- 434-446
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2128471563
- Cited by
- 580
- References
- 51
- FWCI
- 34.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tobin, D. M., Roca, F. J., Oh, S. F., McFarland, R., Vickery, T. W., Ray, J. P., Ko, D. C., Zou, Y., Bang, N. D., Chau, T. T. H., Vary, J. C., Hawn, T. R., Dunstan, S. J., Farrar, J. J., Thwaites, G. E., King, M.-C., Serhan, C. N., & Ramakrishnan, L. (2012). Host Genotype-Specific Therapies Can Optimize the Inflammatory Response to Mycobacterial Infections. Cell. https://doi.org/10.1016/j.cell.2011.12.023
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