Microbial Mechanisms to Escape the Immune System 1

The simultaneous evolution of millions of organisms have resulted in very interesting survival strategies. We already briefly discussed a related subject when we covered the discovery of antibiotics. This time, however, I would like to talk about it from the bug's perspective. How do some of these teeny, tiny microorganisms manage to subvert the immune response of a highly-evolved vertebrate?
Let's take one bacteria as an example, Listeria monocytogenes. I have always been amazed by this bug and the clever mechanisms it uses to infect its host. Granted I spent like 4 years of my PhD program studying it, but that only made it more fun! So first, what kind of bacteria are Listeria (no, this is not a poem...) and why would some people spend 4 years studying it (like me) or even their whole lives (some professors that I know...)?

Listeria colonies in an agar plate in blue; in white other bacteria.
Image from the CDC.
L. monocytogenes is the cause of listeriosis, an infection that can be lethal. It is a facultative anaerobic, Gram-positive bacterium that can be found in soil, water, and other natural elements. Why is it a health risk? Because it can also be found in animal-derived food; it can be present in poultry, cattle, raw milk, dairy products, etc. Not only that, but unlike other microorganisms, it can also grow at 4°C, so it can even contaminate stored food items, making it a bigger problem.

So after it grows, how does Listeria manage to invade its host and escape the immune system of a mammal? Using special proteins (such as Intenalin A and B, InlA/B), Listeria induces its own phagocytosis and once inside a phagocyte, it can lyse the phagosome using another protein, Listeriolisin O (LLO). After being released from the phagosome, it hijacks the cell cytoskeleton, inducing actin polymerization to propel itself inside cytoplasm, again using another bacterial protein, ActA. Once the bacteria reaches the cell membrane, it can actually rupture that cell and spread to a neighboring one directly, without an extracellular phase.

Listeria cell cycle, from the Pasteur Institute.
In red are the bacterial proteins needed for the process.
Listeria also has a number of other mechanisms, like inducing apoptosis in infected cells, promoting secretion of factors from the host cell that will help the bacteria to survive, and traveling to deep lymphoid organs while hiding inside dendritic cells.
Luckily, our immune system has also evolved to fight infections, and we have great tools to defend ourselves from this bacterium. That is exactly the reason why people like me spend years and years studying this bug. Using Listeria, some of the most important mechanisms of defense of our immune system have been unveiled, such as antigen presentation, T cell antigen-specificity and many others1,2. So in the end, we were able to manipulate the villain instead, and use its highly specialized life cycle to improve both our basic and applied knowledge. Listeria has even been used as an experimental vaccine delivery vehicle3. Isn't it a bit ironic that an infectious agent is being used to cure infections!

Batman Returns, Warner Bros.
So if you know of any interesting ways microbes invade other organisms, please let me know. I’ll make sure I comment on that in the next post of this series. In addition, if you would like to read about all the milestones achieved by using Listeria as an infection model in the study of the immune system, I recommend to you the following papers:
  1. Listeria studies lead the way
  2. A brief history of antigen presentation
  3. Listeria as a vaccine delivery vehicle
Contributed by Miguel Tam, PhD.
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