Mycobacterium tuberculosis infection induces complex CD4 T cell responses that include T helper type 1 (Th1) cells and regulatory T cells. Although Th1 cells control infection, they are unable to fully eliminate M. tuberculosis, suggesting that Th1-mediated immunity is restrained from its full sterilizing potential. Investigation into T cell–mediated defense is hindered by difficulties in expanding M. tuberculosis–specific T cells. To circumvent this problem, we cloned CD4+ T cells from M. tuberculosis–infected B6 mice and generated transgenic mice expressing a T cell receptor specific for the immunodominant antigen early secreted antigenic target 6 (ESAT-6). Adoptively transferred naive ESAT-6–specific CD4+ T cells are activated in pulmonary lymph nodes between 7 and 10 d after aerosol infection and undergo robust expansion before trafficking to the lung. Adoptive transfer of activated ESAT-6–specific Th1 cells into naive recipients before aerosol M. tuberculosis infection dramatically enhances resistance, resulting in 100-fold fewer bacteria in infected lungs. However, despite large numbers of Th1 cells in the lungs of mice at the time of M. tuberculosis challenge, protection was not manifested until after 7 d following infection. Our results demonstrate that pathogen-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection.

Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, which limits bacterial replication and facilitates antigen presentation. Here we demonstrate that cells infected with H37Ra became apoptotic after the formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface, followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 through its amino-terminal domain. In macrophages infected with the virulent strain H37Rv, in contrast, the amino-terminal domain of annexin-1 was removed by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M. tuberculosis therefore avoids the host defense system by blocking formation of the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.

Mycobacterium tuberculosis grows in macrophages but escapes these cells by triggering their death. New findings delineate how this pathogen controls macrophage death to favor bacterial survival and avoid host immunity.

Taking antiretroviral drugs at the same time as TB treatment halved the death rate when compared with delaying HIV treatment until after TB treatment was completed, a major South African study has found. Trial investigators announced on September 17th that they have terminated an arm of the study in which patients waited until they had completed TB treatment before starting antiretroviral therapy, because patients in this arm had a significantly higher risk of death.

The skeleton of a man discovered by archaeologists in a shallow grave on the site of the University of York’s campus expansion could be that of one of Britain’s earliest victims of tuberculosis. Radiocarbon dating suggests that the man died in the fourth century. He was interred in a shallow scoop in a flexed position, on his right side. The man, aged 26–35 years, suffered from iron deficiency anaemia during childhood and at 162 centimetres (5ft 4in), was a shorter height than average for Roman males. The first known case of TB in Britain is from the Iron Age (300 BC) but cases in the Roman period are fairly rare, and largely confined to the southern half of England. TB is most frequent from the 12th century AD in England when people were living in urban environments. So the skeleton may provide crucial evidence for the origin and development of the disease in this country.

For the first time in more than 80 years a promising live vaccine against tuberculosis has passed into the clinical phase in Germany: Since Monday of this week the new vaccine, which goes by the designation "VPM1002", has begun safety testing on volunteers in a Phase I clinical trial in Neuss, Germany. It is based on a highly safe vaccine that was introduced in 1921. However, the vaccine has been genetically developed to an extent where it is significantly more effective at preventing infection with tuberculosis bacteria than its predecessor. So far, VPM1002 has proved to be extremely effective and safe in animal models. „ This good protection now has to be proven in humans for the vaccine to be ready for the final approval," explains the Chief Executive Officer of Vakzine Projekt Management GmbH (VPM), Bernd Eisele.