ヒトの結核感染における「謎」

抄録

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy.
There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows:
1. What is the virulence of M. tuberculosis?
2. How does M. tuberculosis persist dormant within the host?
3. What determines the development of disease from remaining healthy after infection with M. tuberculosis?
4. What is the mechanism of “endogenous reactivation” of dormant M. tuberculosis within the host?
5. Can we expect more potent anti-TB vaccine than BCG in near future?
Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all.
What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exertsits detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-α.
How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.