Mycobacterium tuberculosis and immune system evasion

Mycobacterium tuberculosis'' (stained red) in ...

Acid fast stained M. tuberculosis; Image via Wikipedia

In my morning browsing of Science Daily Microbiology, I came across this headline, which describes one of the mechanisms by which the acid-fast bacterium M. tuberculosis is able to persist in the body despite our immune response against the pathogen. The ability of M. tuberculosis to evade the immune system helps to explain the chronic and episodic nature of tuberculosis disease manifestations.

The body normally responds to the presence of many pathogens by recruiting white blood cells, or phagocytes, to the site of infection. These cells then envelop the pathogens, and begin to digest the bacteria with specialized enzymes. This ultimately results in destruction of the pathogen, and clearance of the organisms from the body. There are a number of pathogens that are able to subvert this process though, which leads to our natural defenses being unable to clear an infectious agent. M. tuberculosis is an example of an organism that is able to evade immune system clearance, by blocking the ability of phagocytes to destroy the bacterial cells.

The lower respiratory system receives a constant influx of material from the atmosphere, yet the lobes of the lungs have very few microorganisms present, and there is no normal microbial flora associated with the lower respiratory system. This is in contrast to the upper respiratory system (the bronchiae, for example.) which has a significant number of organisms in the absence of any disease symptoms. This is due to the action of macrophages, a type of white blood cell that constantly moves through the tissue of the lungs searching foreign material that may be present. If a macrophage finds an M. tuberculosis cell though, the bacterium is phagocytosed by the macrophage, but is not killed by the process. The way that the bacterium accomplishes this is actually pretty neat!  Some organisms are able to evade the process of phagocytosis by having a surface that is not amenable to engulfment by a white blood cell, and structures such as the bacterial capsule serve in this role. This is not what happens with TB. When a macrophage contacts an M. tuberculosis cell, it is able to engulf it just fine, however the bacterial cell is able to block the ability of the macrophage to deliver the killing digestive enzymes from cellular organelles called “lysosomes.”

Macrophage containing internalized mycobacteria bacilli

The precise mechanism by which the tuberculosis bacteria are able to do this is not completely clear, but involves a number of specific proteins that virulent strains of the bacterium possess. The end result is that the bacteria get engulfed by macrophages, and then are able to grow inside the macrophage, which in turn allows the bacterium to evade other anti-microbial responses by the body. This means that in many cases, the body is unable to effectively clear the infection once it starts, leading to the chronic nature of many tuberculosis infections.

So back to the Science Daily article: researchers at Linkoping University in Sweden have developed a method for looking at living mycobacteria inside of a macrophage. Note that for the electron micrograph above, the bacterial cells are clearly visible in the picture on the right, but recall that electron microscope is not useful for looking at living cells. The researchers have added a gene for luciferase to the bacterium. This is the same enzyme that causes fireflies to glow, and enables the bacteria to glow when they are inside of a macrophage. It also, unlike many other glowing gene reporters, requires the bacterium to be alive in order to glow. The scientists are now able to visualize and assess the viability of M. tuberculosis cells inside of macrophages, and the amount of light shed corresponds to the number of bacteria inside of a macrophage. It is their hope that they will be able to use this experimental system to rapidly screen potential inhibitors of mycobacteria, either by blocking the ability of the bacterium to prevent phagocytic killing or by blocking the ability of the bacterium to multiply inside macrophages. A long way away from developing a cure for tuberculosis, but a novel way of potentially treating these infections that affect an estimated one third of all the people on Earth.

BONUS: What are some other mechanisms that the human body has for coping with tuberculosis?

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About ycpmicro

My name is David Singleton, and I am an Associate Professor of Microbiology at York College of Pennsylvania. My main course is BIO230, a course taken by allied-health students at YCP. Views on this site are my own.

Posted on March 10, 2011, in Bonus!, Lecture, Microbes in the News. Bookmark the permalink. 4 Comments.

  1. Jessica Melhorn

    One way our body responds to a Tuberculosis infection is by an increase in body temperature. Many microorganisms have a perferred temperature at which they thrive and grow. So our body, in response to infection, will often times raise they body temperature to help destroy these organisms. Another way is if our body has been exposed (even in small amounts that did not cause infection) to any pathogen in the past, the body’s adaptive immune system has a memory of that pathogen. B cells produce and release antibodies which can help prevent or fight infection if the body is even exposed to the pathogen again.

    • We will see at the end of Chapter 16 (Adaptive Immunity) that the memory of TB exposure can be an issue for Health Care Workers, and the ability to easily keep surveillance on workplace exposure.

  2. Steph Weakland

    A receptor on cells, known as “CCR5,” triggers a response to TB and signals to immune cells to attack the organisms. Another way in which the body responds to a TB infection is by building walls around the organisms; however, this inflammation eventually damages the lungs. Also, once the disease reaches the lower respiratory tract, the alveolar macrophage tries to defend the body through the process of phagocytosis.

    • And highly appropriate today, as we introduced “Pattern recognition” in class. CCR5 aids in the non-specific response to a number of different classes of pathogens.

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