Mannose-binding protein B allele confers protection against tuberculous meningitis

Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguou s lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors t hat influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is consider ed 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 defens e, it may under certain circumstances be deleterious to the host. In tuberc ulosis (TB), MBP may assist the spread of this intracellular pathogen. Ther efore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African po pulation in which TB has reached epidemic levels. We found that the MBP B a llele (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 me ningitis (p < 0.002). In addition, we found significantly lower serum MBP c oncentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B al lele affords protection against tuberculous meningitis.