Latent Tuberculosis

Tuberculosis is an infection that is caused by the bacterium Mycobacterium tuberculosis (MTB) and most often affects the lungs (CDC Basic TB Facts). It infects a third of the population worldwide, and in 2014, tuberculosis infected 9.6 million people, killing 1.5 million (CDC Basic TB Facts).  MTB is spread through the air via breathing, coughing, sneezing or speaking (CDC Basic TB Facts). Due to this, tuberculosis is highly contagious when it is in the active form, however it cannot be passed on to someone else if it is in the latent form (CDC Basic TB Facts).

Mycobacterium tuberculosis can only be spread through the air when it is in the active form via breathing, coughing, sneezing, or talking [Image provided by CDC]
Fig. 1: Mycobacterium tuberculosis can only be spread through the air when it is in the active form via breathing, coughing, sneezing, or talking [Image provided by CDC]
MTB can remain dormant so that signs and symptoms remain unexpressed (CDC Basic TB Facts). The problem arises when the MTB becomes active. Many people can live for years with latent tuberculosis without knowing, so it is important to get tested so it can be treated if necessary in order to prevent MTB from becoming active (CDC Basic TB Facts).

The reason why MTB can remain dormant in the lungs is because the body’s immune response has been found to be ineffective when combatting this pathogen. Research has shown that this is due to MTB inducing an increase in interleukin-10 (IL-10), which decreases the production of gamma interferon (Gong et al. 1996). Since gamma interferon is essential for innate immunity, the low levels of gamma interferon caused by MTB infection depress the immune response. The importance of gamma interferon was seen earlier in 1993. An experiment was conducted wherein mice that were gamma interferon-deficient were subjected to MTB, and began to experience extreme liver and spleen necrosis (Flynn et al. 1993).

Another way in which the immune response is ineffective towards MTB is through the disruption of T cell homeostasis. The regulatory T cells CD4+ and CD25+ express the forkhead box P3 (FOXP3), which is essential for maintaining T cell homeostasis and controlling immune response. The percentage of of these regulatory T cells, as well as messenger RNA (mRNA) expression of FOXP3, has been shown to be higher in patients being treated for active tuberculosis when compared to untreated patients with latent tuberculosis. However when grown with MTB secreted antigens ESAT-6 or Ag85B, these regulatory T cells expanded and generated, throwing off the balance, thus inhibiting immune response (Wu et al. 2014).

Effector T cells can also have a hard time mounting an attack against MTB due to an increase in apoptosis of these cells. In a study performed in 2015, it was determined that T cells from patients who tested positive for latent tuberculosis underwent apoptosis at a higher rate than T cells from those who tested negative for latent tuberculosis. Also, it was shown that there was a decrease in the expression of anti-apoptotic genes in latent tuberculosis positive patients than negative ones. Therefore, T cells are dying before they are able to successfully combat MTB (Elliot et al. 2015).

Due to the multiple ways in which MTB can defend itself from the body’s immune response, latent tuberculosis can persist, thus it is important to combat these defenses. The possibility for multiple drug therapies for latent tuberculosis has come to light in numerous experiments that have been conducted. One of the ways in which this has been done is by investigating biosynthetic pathways used by MTB. The biosynthesis of cysteine by MTB is important for its oxidative defense against immune responses. CysM, a cysteine synthase, was previously shown to use O-acetyl-L-serine as a sulfur acceptor in its metabolic pathway. However, is has been determined that another component of the pathway, O-phosphoserine, is also used by CysM as a sulfur acceptor. The development of drug therapies that target not only one part of MTB’s cysteine biosynthetic pathway, but multiple parts, could possibly combat oxidative defense against immune response (Ågren et al. 2008).

Mycobacterium tuberculosis cysteine biosynthetic pathway using O-phosphoserine as a substrate of CysM.(Argen et al. 2008).
Fig. 2: Mycobacterium tuberculosis cysteine biosynthetic pathway using O-phosphoserine as a substrate of CysM. [Argen et al. 2008].
It is important to continue research on latent tuberculosis and MTB because it can greatly withstand the body’s immune response. By finding other sources for its defense mechanism, as well as determining other methods of detection, target drug therapies can be developed in order to combat MTB and latent tuberculosis in order to prevent it from becoming active.

For further reading see…

Annotated Bibliography

12 Replies to “Latent Tuberculosis”

  1. Well composed article on a difficult to understand subject! I especially enjoyed the use of the newer biotechnology and immune response language. Nice job with a tough topic!

    1. Thank you Mrs. Colabroy! I’m glad you liked the language I used, for I was afraid it would be a bit difficult to follow! I appreciate your feedback!

  2. Your summary of the chemistry of latent tuberculosis was logical to follow, but it left me wanting to understand what are the symptoms and dangers of this disease to the person who has it? Is it fatal? how often? What age and demographic is typically affected? I assume the disease causes coughing, due to your explanation of how MTB is contagious, but I don’t really know. Also, as a (completely) non-expert, it would have been nice to have a sentence about what function the T cell has in our bodies, bringing more importance to MTB interfering with their function. This would have brought more understanding to how the disease is being treated.

    1. Thank you for your feedback Ben! I will be adding additional pages that explore different areas of the disease, one of which will include signs and symptoms, and how it is spread. However, it wouldn’t be a bad idea to briefly introduce some of this important information on this page! I will be sure to do that! As far as the function of the T cells in the body, The phrase is linked to the biochemistry primer, which gives a definition and another link to a page with more information on T cells. Let me know if you’re having trouble getting to the biochemistry primer and I will see if I can reset the hyperlink. Also, more information on how the T cells interact with MTB will be discussed further, as well as associated treatments, in the additional pages, so be sure to watch this space for updates! Thanks again for your input!

  3. The hyperlinks were extremely useful, but the most clear explanations you wrote were the ones which first introduced the topic, then gave it a bit of context, and then explained its relevance to the specific topic. Examples of this are paragraphs two and four. Overall, your logical structure made it easy to follow, which allowed me to spend more effort keeping up with what you’re saying.

    1. Thank you Emma! I’m glad that you were able to follow my explanations! I tend to sometimes cram a lot of information in a short amount of space, so I appreciate your feedback. I will definitely go back and try to make the other paragraphs follow the same structure as paragraphs two and four since those seem to be the most easily understood!

  4. I found your summary concerning latent tuberculosis very interesting and insightful. The opening paragraph is especially helpful to understanding the subject as you open the subject with a simple and easily-understood explanation of the disease. The following paragraphs elaborate on this simple explanation, which helps relay more complex features of the disease. Overall, your article on latent tuberculosis was very educational, however some questions still remain of latent tuberculosis. Perhaps you could add statistics of the disease’s impact around the world to show fatalities and survivals of the infected.

    1. Thanks Alex! As I mentioned in my previous reply to Ben, I will elaborate more on numbers and statistics in the additional pages that will follow this one. However, seeing as this is a title page, it would be wise to briefly mention how widespread and fatal it is. I appreciate your feedback, and I’m glad that you found it understandable and educational! That’s the goal!

  5. This was a very interesting read. The links to the biochemistry primer for the scientific words were helpful to understand at times there were so many in a row that it was difficult to understand.

    1. Thank you for your feedback Jack! I was a bit worried about that when I initially posted this page. I will definitely go back and see if I can break it down and bit more so there isn’t a lot of new vocabulary in a row.

  6. This article was easy to read and I found I wanted to learn more on the subject, similar to other comments made. The links to the primer were necessary for me but did not distract from understanding the complexity of the subject matter.

    1. Thanks Maryanne! As I mentioned before in my other replies, this is only the beginning for this post; I will be adding additional pages that will further explore different areas of this disease, such as how it affects metabolic processes in the body, and treatment. Be sure to watch this space for more information! Again, thank you for your feedback!

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