Immunological basis of early clearance of Mycobacterium tuberculosis
infection: the role of natural killer cells
Abstract
Tuberculosis kills more people than any other single infectious disease
globally. Despite decades of research, there is no vaccine to prevent TB
transmission. Bacille Calmette-Guerin (BCG) vaccine developed a century
ago has little effect on pulmonary TB and does not control transmission.
Lack of an effective vaccine emanates from lack of knowledge on
correlates of protective immunity on which to base vaccine design and
development. However, some household contacts who are extensively
exposed to Mtb infection remain persistently negative to tuberculin skin
test and interferon-gamma assay. These individuals called “resisters”
clear Mtb infection early before the development of acquired immunity.
The immunological basis of early Mtb clearance is yet to be established,
however, innate lymphocytes such as monocytes/macrophages, dendritic
cells, neutrophils and natural killer cells, and innate like T cells
such as mucosal associated invariant T cells, invariant natural killer T
cells and gamma-delta (γδ) T cells have been implicated in this early
protection. One of the cells that has attracted increasing attention in
recent years, in protection against Mtb is the natural killer cell.
Emerging data from animal and epidemiological studies indicate that NK
cells may play a significant role in the fight against Mtb. NK cells
express various surface markers to recognize and kill both Mtb and
Mtb-infected cells. In this review, recent advances in our understanding
of NK cells in the fight against Mtb early during infection, with
emphasis on cohort studies, will be presented.