Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Mannose-binding lectin alleles in sub-Saharan Africans and relation with susceptibility to infections

Genes & Immunity volume 4, pages 362–367 (2003)Cite this article

Abstract

Mannose-binding lectin (MBL) plays an important role in the early stages of primary infections and during the decay of maternal antibodies in infants. Various studies have looked at the relation between serum MBL concentrations, MBL gene alterations and susceptibility to infections. We investigated the distribution of variant MBL alleles in 626 unrelated adults from sub-Saharan African countries and looked for a potential relation between these alleles and the incidence, prevalence and death rate of tuberculosis for sub-Saharan Africa. We also evaluated the relation between MBL genotypes and susceptibility to HIV-1 infection in 188 Gabonese adults. We found that (i) the prevalence of the common variant MBL alleles is correlated with the incidence of tuberculosis in sub-Saharan Africa (r=0.565), (ii) the mutant MBL G57E allele, in either the homozygous or compound heterozygous state, is associated with susceptibility to HIV-1 infection in the Gabonese population (P=0.019).Our data plus those in the literature suggest that individuals who are homozygous for the mutant MBL alleles display increased susceptibility to infections. Interestingly, we found that individuals who are heterozygous for MBL mutations are much less susceptible to infections than those who are homozygous for the wild-type MBL allele.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Sastry K, Herman GA, Day L et al. The human mannose-binding protein gene. J Exp Med 1989; 170: 1175–1189.

    Article  CAS  Google Scholar 

  2. Taylor ME, Brickell PM, Craig RK, Summerfield JA . Structure and evolutionary origin of the gene encoding a human serum mannose-binding protein. Biochem J 1989; 262: 763–771.

    Article  CAS  Google Scholar 

  3. Kuhlman M, Joiner K, Ezekowitz RAB . The human mannose-binding protein functions as an opsonin. J Exp Med 1989; 169: 1733–1745.

    Article  CAS  Google Scholar 

  4. Matsushita M, Fujita T . Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med 1992; 176: 1497–1502.

    Article  CAS  Google Scholar 

  5. Turner MW . Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today 1996; 17: 532–540.

    Article  CAS  Google Scholar 

  6. Super M, Thiel S, Lu J, Levinsky RJ, Turner MW . Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet 1989; i: 1236–1239.

    Article  Google Scholar 

  7. Sumiya M, Super M, Tabona P et al. Molecular basis of opsonic defect in immunodeficient children. Lancet 1991; 337: 1569–1570.

    Article  CAS  Google Scholar 

  8. Lipscombe RJ, Sumiya M, Hill AVS et al. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1992; 1: 709–715.

    Article  CAS  Google Scholar 

  9. Madsen HO, Garred P, Kurtzhals JAL et al. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics 1994; 40: 37–44.

    Article  CAS  Google Scholar 

  10. Madsen HO, Garred P, Thiel S et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995; 155: 3013–3020.

    CAS  PubMed  Google Scholar 

  11. Garred P, Madsen HO, Kurtzhals JAL et al. Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in Black Africans. Eur J Immunogenet 1992; 19: 403–412.

    Article  CAS  Google Scholar 

  12. Hoal-Van Helden EG, Epstein J, Victor TC et al. Mannose-binding protein B allele confers protection against tuberculous meningitis. Pediat Res 1999; 45: 459–464.

    Article  CAS  Google Scholar 

  13. Bellamy R, Ruwende C, Mcadam KPWJ et al. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. Q J Med 1998; 91: 13–18.

    Article  CAS  Google Scholar 

  14. Ezekowitz RAB, Kuhlman M, Groopman JE, Byrn RA . A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med 1989; 169: 185–196.

    Article  CAS  Google Scholar 

  15. Garred P, Madsen HO, Balslev U et al. Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 1997; 349: 236–240.

    Article  CAS  Google Scholar 

  16. Prohaszka Z, Thiel S, Ujhelyi E, Szlavik J, Banhegyi D, Fust G . Mannan-binding lectin serum concentrations in HIV-infected patients are influenced by the stage of disease. Immunol Lett 1997; 58: 171–175.

    Article  CAS  Google Scholar 

  17. Dye C, Scheele S, Dolin P, Pathania V, Raviglione . Global burden of tuberculosis: estimated incidence, prevalence and mortality by country. JAMA 1999; 282: 677–686.

    Article  CAS  Google Scholar 

  18. Lipscombe RJ, Beatty DW, Ganczakowski M et al. Mutation in the human mannose-binding protein gene: frequencies in several population groups. Eur J Hum Genet 1996; 4: 13–19.

    Article  CAS  Google Scholar 

  19. Madsen HO, Satz ML, Hogh B, Svejgaard A, Garred P . Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. J Immunol 1998; 161: 3169–3975.

    CAS  PubMed  Google Scholar 

  20. Lapouméroulie C, Acuto S, Rouabhi F, Labie D, Krishnamoorthy R, Bank A . Expression of a beta thalassemia gene with abnomal splicing. Nucleic Acids Res 1987; 15: 8195–8204.

    Article  Google Scholar 

  21. Garred P, Richter C, Andersen AB et al. Mannan-binding lectin in the sub-Saharan HIV and tuberculosis epidemics. Scand J Immunol 1997; 46: 204–208.

    Article  CAS  Google Scholar 

  22. Schorey JS, Carroll MC, Brown EJ . A macrophage invasion mechanism of pathogenic mycobacteria. Science 1997; 277: 1091–1093.

    Article  CAS  Google Scholar 

  23. Garred P, Harboe M, Oettinger T, Koch C, Svejgaard A . Dual role of mannan-binding protein in infections: another case of heterosis? Eur J Immunogenet 1994; 21: 125–131.

    Article  CAS  Google Scholar 

  24. Santos IK, Costa CH, Krieger H et al. Mannan-binding lectin enhances susceptibility to visceral leishmaniasis. Infect Immun 2001; 69: 5212–5215.

    Article  CAS  Google Scholar 

  25. Saifuddin M, Hart ML, Gewurz H, Zhang Y, Spear GT . Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1. J Gen Virol 2000; 81: 949–955.

    Article  CAS  Google Scholar 

  26. Maas J, de Roda Husman AM, Brouwer M et al. Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. AIDS 1998; 12: 2275–2280.

    Article  CAS  Google Scholar 

  27. Neonato MG, Lu CY, Guilloud-Bataille M et al. Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections. Eur J Hum Genet 1999; 7: 679–686.

    Article  CAS  Google Scholar 

  28. Garred P, Madsen HO, Hofmann B, Svejgaard A . Mannose-binding protein genotypes and recurrent infection. Lancet 1995; 346: 1629–1630.

    Article  Google Scholar 

  29. Summerfield JA, Ryder S, Sumiya M et al. Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet 1995; 345: 886–889.

    Article  CAS  Google Scholar 

  30. Matsushita M, Hijikata M, Ohta Y et al. Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL. Arch Virol 1998; 143: 645–651.

    Article  CAS  Google Scholar 

  31. Garred P, Madsen HO, Halberg P et al. Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus. Arthritis Rheum 1999; 42: 2145–2152.

    Article  CAS  Google Scholar 

  32. McBride MO, Fischer PB, Sumiya M et al. Mannose-binding protein in HIV-seropositive patients does not contribute to disease progression or bacterial infections. Int J STD AIDS 1998; 9: 683–688.

    Article  CAS  Google Scholar 

  33. Gabolde M, Muralitharan S, Besmond C . Genotyping of the three major allelic variants of the human mannose-binding lectin gene by denaturing gradient gel electrophoresis. Hum Mutat 1999; 14: 80–83.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank N Gerard, M Makuwa and C Tevi-Benissan for providing DNA samples, F Lekoulou, R Moukagni, A Moussavou, R Nabias and J Lansoud-Soukate for assistance with the field work, and A Luty for reading the manuscript. We are indebted to the subjects and especially the HIV patients for their participation in this study. This study was funded by INSERM and by the Centre International de Recherches Médicales (CIRMF-Gabon), which is supported by the Government of Gabon, ELF-Gabon and the Ministère Français des Affaires Etrangères.

Author information

Authors and Affiliations

  1. Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon

    L E Mombo, C Y Lu, S Ossari, I Bedjabaga & L Sica

  2. Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Paris, France

    L E Mombo, R Krishnamoorthy & C Lapoumeroulie

Authors
  1. L E Mombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Y Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Ossari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I Bedjabaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Krishnamoorthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Lapoumeroulie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L E Mombo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mombo, L., Lu, C., Ossari, S. et al. Mannose-binding lectin alleles in sub-Saharan Africans and relation with susceptibility to infections. Genes Immun 4, 362–367 (2003). https://doi.org/10.1038/sj.gene.6363979

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363979

Keywords

This article is cited by

Search

Advanced search

Quick links