Macrophage mutation causes susceptibility to tuberculosis

A mutation in macrophages — a key immune cell — pre-disposes patients to infection with weakly virulent bacteria reports a paper online in Nature Immunology this week. The work suggests that these mutations could lead to increased susceptibility to tuberculosis.

Jean-Laurent Casanova and colleagues identified two groups of patients who had heightened susceptibility to tuberculosis following administration of the widely-used tuberculosis BCG vaccine. The susceptibility was tracked to a mutation in a gene controlling the so-called ‘respiratory burst’ which is normally required for the destruction of bacteria. The mutation specifically affected the respiratory burst in macrophages following their engulfment of tuberculosis bacteria in the BCG preparation.

This study demonstrates that that the respiratory burst in human macrophages is a crucial mechanism for protective immunity against tuberculosis.