Refocusing on Leprosy
Posted on 2019-05-08
The Leprosy Dichotomy
Leprosy, also known as Hansen’s disease, was once greatly feared throughout history. Biblical references to so-called “lepers” made the disease out to be a curse of uncleanliness, whilst medieval lepers were ostracised and either lived as monks in hermitages or as beggars in the streets. It wasn’t until the mid-20th century that leprosy could be successfully cured using a cocktail of antibiotics. Despite this, patients in many parts of the world are still segregated from their peers, despite the low transmission rates of the bacterium.
There are two main reactions to a Mycobacterium leprae or lepromatosis infection; tuberculoid, and lepromatous. (Literature often makes reference to a third type, “borderline leprosy”, which indicates an intermediate state that usually develops into either tuberculoid or lepromatous types). Interestingly, these reactions are not driven by the bacterium, but rather by the host. The key difference between these disease manifestations is the T helper cell response. Th1 cells are associated with the milder tuberculoid disease, with fewer skin lesions and the possibility of making a near-full recovery over time. Th2 cells are dominant in the more serious lepromatous form, which causes the well-known deformities and typically leads to a shortened lifespan.
With a Th1 response, the immune system is better suited to target intracellular pathogens – pathogens such as M. leprae. The main advantage for the host with tuberculoid leprosy is the activation of large numbers of macrophages, which can kill infected cells as well as directly phagocytose any bacteria found outside. Th1 cells also promote the proliferation of cytotoxic T cells, which kill infected cells. The production of nitric oxide by Th1 cells is also important, as the bacterium is unusually susceptible to this chemical. While the infection is still capable of forming lesions, these are few in number and cause limited damage to the surrounding tissue.
A Th2 response is a different story. The all-important macrophage response is dampened by Th2 cells as a direct result of TGF-ß production. In these instances, a humoral B cell response is favoured, with large volumes of antibodies being produced which provide little immune support. Without macrophages and cytotoxic T cells to kill infected cells, the bacteria are free to spread, causing skin lesions, destroying nerves, contributing to deformity via the absorption of cartilage, and impairing the function of various vital organs.
Whilst the disease caused by these bacteria has caused human suffering for millennia, it has also made significant contributions to the field of immunology. Not only has leprosy helped distinguish the Th1/Th2 pathways, but it also helped characterise novel T helper cell subsets, including Th9 and Th22. There is still more research to be done, however; much about the disease is still unknown, and there are always improvements to be made in its treatment.
Further reading:
T-Cell Regulation in Lepromatous Leprosy
Product suggestions:
abx153237 -TBX21 (Th1 cell transcription factor) sandwich ELISA
abx151632 -GATA3 (Th2 cell transcription factor) sandwich ELISA
abx595963 -FOXO1 (Th9 cell transcription factor) cell ELISAabx266374 Mycobacterium leprae peptide