Mycolic acid-specific T cells protect against Mycobacterium tuberculosis infection in a humanized transgenic mouse model

摘要

Most cases of tuberculosis are caused by a bacterium called Mycobacterium tuberculosis, which is believed to have infected one third of the world’s population. Most of these infections are dormant and don’t cause any symptoms. However, active infections can be deadly if left untreated and often require six months of treatment with multiple antibiotics. One reason why these infections are so difficult to treat is because the M. tuberculosis cell walls contain fatty molecules known as mycolic acids, which make the bacteria less susceptible to antibiotics. These molecules also help the bacteria to subvert and then hide from the immune system. The prevalence of the disease and the increasing problem of antibiotic resistance have spurred the search for an effective vaccine against tuberculosis. While most efforts have focused on using protein fragments in tuberculosis vaccines, some evidence suggests that human immune cells can recognize fatty molecules such as mycolic acids and that these cells could help manage and control M. tuberculosis infections. However, it has been difficult to determine whether these immune cells genuinely play a protective role against the disease because most vaccine research uses mouse models and mice do not have an equivalent of these immune cells. Now, Zhao et al. have engineered a “humanized” mouse model that produces the fatty molecule-specific immune cells, and show that these mice do respond to the presence of mycolic acids. Infecting the genetically engineered mice with M. tuberculosis revealed that the fatty molecule-specific immune cells were quickly activated within lymph nodes at the center of the chest. These cells later accumulated at sites in the lung where the bacteria reside, and ultimately protected against M. tuberculosis infection. The results show that these specific immune cells can counteract M. tuberculosis, and highlight the potential of using mycolic acids to generate an effective vaccine that provides protection against tuberculosis.