Mol Immunol. 2007 Mar;44(9):2213-20. Epub 2006 Dec 6.Click here to read Links
Influence of candidate susceptibility genes on tuberculosis in a high endemic region.
Søborg C, Andersen AB, Range N, Malenganisho W, Friis H, Magnussen P, Temu MM, Changalucha J, Madsen HO, Garred P.
Tissue Typing Laboratory of the Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein (SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting. Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included. Polymorphisms in the candidate genes were detected by different PCR-based techniques. A significant association between pulmonary tuberculosis and a microsatellite marker in the 5'(CA)n locus in the SLC11A1 gene compared with controls (38% versus 30% odds ratio 1.45, 95% CI: 1.06-1.9, P=0.014) was observed. The association was apparent only in HIV negative tuberculosis patients. No association with tuberculosis was seen with 3 other SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with MBL2 and VDR polymorphisms. The tuberculosis associated microsatellite marker was situated on different SLC11A1 haplotypes. In this cohort a microsatellite marker in the 5'(CA)n locus situated in the SLC11A1 gene was associated with tuberculosis. The observed association was seen only in HIV negative patients suggesting that this genetic susceptibility for tuberculosis may be surpassed by co-infections.
Human macrophage host defense against Mycobacterium tuberculosis 2008
Tuberculosis has plagued humans for ages, and understanding the host defense mechanisms against this pathogen has been a challenge to immunologists for decades. In mouse models of tuberculosis infection, the role of nitric oxide in antimicrobial activity is well defined. Recent studies indicate a role for the induction of autophagy in host defense against mycobacterial infection. In human macrophages, vitamin D-mediated induction of antimicrobial peptides appears to be an important player in combating Mycobacterium tuberculosis. Further understanding these defense mechanisms in human tuberculosis will help the development of new interventional strategies to prevent and treat disease.