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Influence of mannose-binding lectin on HIV infection and tuberculosis in a Western-European population.

Garcia-Laorden MI, Pena MJ, Caminero JA, Garcia-Saavedra A, Campos-Herrero MI, Caballero A, Rodriguez-Gallego C

Department of Immunology and RedRespira-ISCiii-RTIC-03/11, Hospital de Gran Canaria Dr. Negrin, Barranco de la Ballena s/n 35010, Las Palmas de Gran Canaria, Spain.

Mannose-binding lectin (MBL) is a serum lectin that mediates phagocytosis and activates complement. Its deficiency has been associated with increased susceptibility to infectious diseases, mainly in childhood. However, non-producer mbl-2 alleles are common in most populations, suggesting a selective advantage of these alleles. We have analysed the association of mbl-2 structural and promoter polymorphisms with HIV infection and tuberculosis (TBC) in a white Spanish population, including 615 HIV patients with and without TBC, 127 no-HIV TBC patients, 142 TBC household contacts and 344 controls. The frequency of low or non-producer mbl-2 genotypes was lower in HIV patients than in controls. HIV-TBC patients presented lower frequencies of low or non-producer alleles and genotypes than HIV no-TBC patients and controls. Additionally, we found a significantly positive correlation between the incidence of TBC and the frequency of non-producer mbl-2 alleles in Western Europe. Therefore, MBL deficiency may be associated with a lower risk of HIV infection, and also of active TBC, at least in HIV patients. The protective role of low-producer mbl-2 genotypes against TBC together with the positive correlation observed between non-producer mbl-2 alleles and TBC incidence, suggest a balancing selection: in spite of an increased susceptibility to respiratory infections associated with MBL deficiency, mbl-2 deficient alleles would have been selected along different populations as a consequence of its selective advantage against intracellular pathogens, such as M. tuberculosis.

Published 12 June 2006 in Mol Immunol, 43(14): 2143-50.
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