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Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis
journal contribution
posted on 2023-06-08, 17:10 authored by Agnes A Awomoyi, Arnaud Marchant, Joanna M M Howson, Keith P W J McAdam, Jenefer M Blackwell, Melanie NewportMelanie NewportHost genetic factors are major determinants of susceptibility to tuberculosis, and an understanding of the molecular basis of this observation has major implications for the development of novel therapies and vaccines. Slc11a1 (formerly Nramp1), the first murine infection susceptibility locus identified, regulates early innate responses to intracellular pathogens. Variation in the human homologue SLC11A1 is associated with and linked to tuberculosis in genetically different populations. In a case-control study of 329 tuberculosis case patients and 324 control subjects, the association between allele 2 of a functional SLC11A1 polymorphism and tuberculosis has been reproduced. This variant is associated with higher lipopolysaccharide-induced production of the macrophage-deactivating cytokine interleukin-10. Furthermore, monocytes from persons who develop tuberculosis innately produce more interleukin-10 than do monocytes from healthy control subjects. These data therefore confirm the importance of SLC11A1 in tuberculosis susceptibility in humans and suggest that SLC11A1 influences tuberculosis susceptibility by regulation of interleukin-10.
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Publication status
- Published
Journal
Journal of Infectious DiseasesISSN
0022-1899Publisher
Oxford University PressExternal DOI
Issue
12Volume
186Page range
1808-1814Department affiliated with
- Global Health and Infection Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2014-05-08Usage metrics
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