Abstract and Introduction
Abstract
Mycobacterium tuberculosis was one of the first human pathogens to be identified as the cause of a specific disease – TB. TB was also one of the first specific diseases for which immunotherapy was attempted. In more than a century since, multiple different immunotherapies have been attempted, alongside vaccination and antibiotic treatment, with varying degrees of success. Despite this, TB remains a major worldwide health problem that causes nearly 2 million deaths annually and has infected an estimated 2 billion people. A major reason for this is that M. tuberculosis is an ancient human pathogen that has evolved complex strategies for persistence in the human host. It has thus been long understood that, to effectively control TB, we will need to address the ability of the pathogen to establish a persistent, latent infection in most infected individuals. This review discusses what is presently known about the interaction of M. tuberculosis with the immune system, and how this knowledge has been used to design immunotherapeutic strategies.
Introduction
Mycobacterium tuberculosis, the causative agent of TB, is one of the world's most devastating human pathogens. In 2010, there were an estimated 8.8 million incident cases of TB and approximately 1.5 million deaths.[1] Central to the success of M. tuberculosis as a pathogen is its ability to persist within humans for long periods in a clinically latent state; approximately 95% of the people who become infected develop a latent infection. The magnitude of this disease reservoir is estimated to be approximately 2 billion people or approximately a third of the global population.[2] The global burden of disease has been worsened by the spread of HIV:[3,4] the two diseases form a vicious cycle with each worsening the outcome of the other.[5–7] Finally, the spread of multidrug-resistant TB (MDR-TB; defined as a strain of M. tuberculosis that is resistant to at least isoniazid and rifampin, the two drugs that have been the backbone of most treatment regimens) and extremely drug-resistant TB (XDR-TB; defined as resistance to isoniazid and rifampin plus resistance to important second-line medications: the fluoroquinolones and at least one of the aminoglycosides, such as amikacin, kanamycin or capreomycin) has sharply raised interest in better therapies for TB.[8] All of this continues to make TB control a priority issue around the globe.
This review introduces the disease, particularly the complex interaction of M. tuberculosis with the host's immune system, as background to understanding the challenges that immunotherapy faces and some of the different approaches that have been tried.
Immunotherapy. 2012;4(6):629-647. © 2012 Future Medicine Ltd.
