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Mannose-binding protein B allele confers protection against tuberculous meningitis
E G Hoal-Van Helden1, J Epstein, T C Victor
1Department of Medical Biochemistry and MRC Centre for Molecular and Cellular Biology, University of Stellenbosch, Tygerberg, South Africa.
Abstract:
Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguous lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors that influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP plays a role in first-line host defense, it may under certain circumstances be deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African population in which TB has reached epidemic levels. We found that the MBP B allele (G54D), which disrupts the collagen region of the protein and results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative controls from the same community, compared with 12 of 91 (13%) of the patients with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous meningitis (p < 0.002). In addition, we found significantly lower serum MBP concentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B allele affords protection against tuberculous meningitis.
Insights
Low levels of mannose-binding protein (MBP), a key immune protein, appear protective against tuberculosis meningitis. Specific MBP genotypes associated with reduced MBP may offer defense against this severe TB complication.
Area of Science:
- Immunology
- Infectious Diseases
- Genetics
Background:
- Tuberculosis (TB) primarily affects the lungs, but can spread to the meninges, especially in children.
- Host factors influencing tuberculous meningitis (TBM) development are not fully understood.
- Mannose-binding protein (MBP) is an innate immune protein that binds Mycobacterium tuberculosis and can act as an opsonin.
Purpose of the Study:
- To investigate the role of mannose-binding protein (MBP) genotypes in susceptibility to tuberculous meningitis (TBM).
- To test the hypothesis that MBP genotypes associated with low MBP levels are protective against TBM.
Main Methods:
- Genotyping of MBP alleles in a South African population with high TB prevalence.
- Comparing MBP allele frequencies in TB-negative controls, pulmonary TB patients, and TBM patients.
- Measuring serum MBP concentrations in TB-negative controls and recovered TB patients.
Main Results:
- The MBP B allele (G54D), linked to low MBP levels, was significantly less frequent in pulmonary TB and TBM patients compared to TB-negative controls.
- Individuals with the MBP B allele showed a reduced risk of developing TBM.
- Lower serum MBP concentrations were observed in TB-negative controls compared to recovered TB patients.
Conclusions:
- The MBP B allele appears to confer protection against the development of tuberculous meningitis.
- MBP genotype may be a significant host factor influencing TBM susceptibility.
- Further research into MBP's role in TB pathogenesis is warranted.