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Meningitis vs the immune system: kill or be killed

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This post was chosen as an Editor's Selection for ResearchBlogging.orgNeisseria meningitidis is a very nasty bug that can cause life-threatening bacterial meningitis; however, many people have the bacteria living harmlessly in their nasopharynx (the area at the back of your nose). The problems begin when the bacteria enter the bloodstream, after which rapid disease progression is likely. Even if it’s not fatal, meningitis can have serious consequences, including deafness or limb amputation. The specific warning signs that can help you identify a N. meningitidis infection are definitely worth a read.

The bacterium is not only nasty but also very crafty. I’ve been reading a paper from PLoS ONE that explains how it can evade being destroyed by macrophages, the ‘first line of defence’ for the body’s immune system. These immune cells engulf invading bacteria through a process known as phagocytosis. The bacteria are then broken down inside the macrophage using a series of enzymes and toxic molecules, and the broken fragments of microbe are passed on to specialised immune cells that attack any remaining bacteria.

Stopping the macrophages doing their job is an important step for an invading pathogen. Some bacteria, such as Mycobacterium tuberculosis, do this by preventing the macrophages breaking them down. They get engulfed, but they just stay dormant and hide within the immune cells until they’re ready to emerge and cause the tuberculosis disease. N. meningitidis has a very different tactic: it makes the macrophages commit suicide. The proper name for this is apoptosis, or ‘programmed cell death’, a very important cellular pathway that usually happens in a highly regulated manner (you don’t want your cells dying for no reason).

The key to this is a protein found on the outer surface of the bacteria, with the snappy title ‘Neisseria hia/hsf homologue A’, or NhhA for short. This protein is used as an anchor, sticking the bacteria to the body’s epithelial cells. Without NhhA, for example, N. meningitidis is unable to colonise mouse nasal cavities.

NhhA is also able to bind to macrophages, and this greatly increases their rate of apoptosis. The group tested different chemical pathways that can result in cell death and concluded that caspase activation is the root of the apoptosis. Caspases are proteases, and their job is to break down other proteins. In bacteria lacking NhhA, apoptosis of macrophages was seen at a much lower rate.

This work gives an insight into the way N. meningitidis evades the immune system – essentially, by killing macrophages before they can engulf and kill the N. meningitidis bacteria. Given the severity of the disease caused by these bacteria, this new information is very welcome.

Benjamin Thompson

Sjölinder M, Altenbacher G, Hagner M, Sun W, Schedin-Weiss S, & Sjölinder H (2012). Meningococcal Outer Membrane Protein NhhA Triggers Apoptosis in Macrophages. PloS one, 7 (1) PMID: 22238624

Image Credit: Sanofi Pasteur on Flickr
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Written by Benjamin Thompson

13/02/2012 at 6:00 pm

Posted in Disease

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One Response

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  1. [...] Neisseria meningitidis, a bacterium that can cause life-threatening meningitis, lives harmlessly in the nasopharynx of many people. The same bacterial protein that allows is to adhere to epithelial cells also induces apoptosis in macrophages, allowing Neisseria to avoid destruction. [...]


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