Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis - 09/05/15
, Luis C. Berrocal-Almanza a , Shruthi Thada a, b , Surabhi Goyal b, c , Hortense Slevogt c , Gaddam Sumanlatha b , Abid Hussain b , Saubashya Sur a , Sanne Burkert a , Djin-Ye Oh a, d , Vijayalakshmi Valluri e , Ralf R. Schumann a , Melanie L. Conrad a, f, ⁎ Summary |
Background |
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (MTB) infection, is still a global public health problem. TB susceptibility varies greatly in infected individuals, and mycobacterial recognition by the innate immune system likely affects disease course and outcome. This research describes a single nucleotide polymorphism in the Toll-like receptor (TLR) 1 gene that functionally alters the innate immune response to MTB and is associated with TB susceptibility in India.
Methods |
206 TB patients and 239 healthy controls from Hyderabad, India were analyzed for SNPs in the TLR1 and TLR2 genes, which were subsequently correlated to TB susceptibility. To test individual responses to MTB lysates, we stimulated PBMCs from genotyped healthy German individuals, as well as HEK cells transfected with TLR1/2 variants. TNF production and NF-kB activation were assessed respectively.
Results |
Cohort analysis associated the TLR1-248N SNP (RS4833095) with TB protection. TLR1-248N expressing PBMCs from healthy controls exhibited an increased TNF response to MTB lysates. In addition to this, functional studies using HEK cell lines transfected with TLR1-248N and stimulated with MTB showed an increased NF-kB activation.
Conclusion |
SNP TLR1-248N is associated with TB protection in an Indian population and exhibits an increased immune response to MTB lysate in vitro.
Le texte complet de cet article est disponible en PDF.Keywords : Toll-like receptor 1, Mycobacterium tuberculosis, Single nucleotide polymorphism, India, Modeling, Functional analysis
Abbreviations used : BCG, CI, DNA, ELISA, HEK, LD, LPS, MTB, NF-κB, OR, PBMC, PCR, RMSD, SNP, TB, TLR, TNF
Plan
| ☆ | The work for this paper was carried out in Hyderabad, Andhra-Pradesh, India and Berlin, Germany. |
| ☆☆ | Parts of this work have been presented at: 1. DGfI/SIICA Joint Annual Meeting (September 28 – October 1 2011, Riccione, Italy). 2. Keystone Symposium (May 10–15 2013, Ouro Preto, Brazil), The Innate Immune Response in the Pathogenesis of Infectious Disease. |
Vol 95 - N° 3
P. 328-335 - mai 2015 Retour au numéro
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