As an
ancient microbe, Mycobacterium tuberculosis (MTB) is an extremely successful
pathogen. MTB causes more deaths worldwide now than at any previous time in
history as the World Health Organization (WHO) estimates that approximately
one-third of the world’s population (roughly 2 billion total) is infected with
MTB. MTB is a major health threat, causing 9 million new infections and between
2 and 3 million deaths annually. Future prospects look bleak due to the
increasing impact of HIV and drug resistance MTB strains (MDR) on the TB
epidemic.
The clinical course of TB provides clues as to
the mechanisms that underlie MTB’s success as a pathogen. First, MTB
establishes infection with a small inoculum, suggesting that it inhibits innate
immune responses. Second, it often persists throughout the life of the host, suggesting evasion of adaptive immunity. Third, the transmission of MTB from one host to another typically depends upon the formation of lung cavities in which aerosols are generated by coughing or sneezing.
The mechanisms of lung
cavitation are complex but include bystander damage of healthy tissue by the
host cellular immune response. It is generally thought that granuloma formation
is a means by which the host controls certain pathogens, most notably mycobacteria
and fungal species. Granulomas form in animal models of TB and in human
infection the scarred result of the granulomatous response to initial infection
is sometimes observed as a calcified lesion abutting the pleural in a lower
lobe of the lung, the “Ghon lesion”. Although the granuloma limits the extent
of early infection, it is ultimately cell-mediated immunity involving T-cells
that control MTB replication.
