Macrophages are effective weapons used by our immune system to absorband digest pathogenic intruders. Some bacteria, however, can subvertthis defence mechanism and even multiply within the macrophages. Cellbiologists at the University of Bonn have revealed such a strategy in arecently publication in the journal 'Traffic' (Vol. 6, No. 8, August2005, pp.635-653). Their findings reveal that the pathogens escape the'stomach' of the macrophages which might otherwise digest them.
Action stations in the horse's lung! A bacterium has just beeninhaled into a horse's bronchial tubes, and immune cells are quicklyrecruited to the spot to neutralise the intruder. Macrophages, cellswhose job is to devour such intruders, are attracted by substancestypical of bacteria, which surround the microbe like a cloud. As soonas the immune cells have detected the intruder, they cover thebacterium with part of their own cell membrane like a hood, creating amembrane sac in which the intruder is trapped. This 'phagosome' (fromGreek phagein = to eat) cuts itself off into the inside of themacrophage and is now the point on which all the macrophage's offensiveweaponry is concentrated: the phagosome is flooded with oxygen radicalsand acid. Another kind of membrane bags, the lysosomes, merge with thephagosome and confront the microbe with highly reactive digestiveenzymes. A few hours after the first alarm bells have rung there isnothing left of the bacterium, and the potential danger has beeneliminated.
Multiplication inside the killer
This is what normally happens. However, a whole range ofpathogens have become specialised in tricking this very part of thedefence mechanism and survive or even multiply in these macrophageswhich are actually supposed to kill them.
One of these pathogens is Rhodococcus equi. This bacterium cancause a lung disease in young foals which is very similar totuberculosis in humans. Hence, it is not too surprising thatRhodococcus equi is closely related to the tubercle bacillus(Mycobacterium tuberculosis). Since macrophages are the main target ofRhodococcus in the horse's lung, a lot of rhodococci are found thereduring an infection.
In the Bonn Institute of Cell Biology Eugenia Fernandez andMarco Polidori in Professor Albert Haas's team have been examining whyRhodococcus equi is not killed and digested in macrophages, and is evenable to multiply there. In the course of this study the group was ableto demonstrate that the rhodococci are able to put prevent thephagosome development inside the macrophage, preventing acidificationand merging with the lysosomes. As a result the bacteria are notexposed to the large array of lysosomal digestive enzymes and acid.
Killing the killer
'Basically what this means is that the rhodococci manipulatetheir host cell, they make it themselves comfartable in an environmentfree of acid and digestive enzymes and multiply there,' Professor Haascomments. Within a few days after the onset of the infection, themacrophages die of the infection, they disintegrate and release themultiplied pathogens.
The Bonn cell biologists have demonstrated in the past thatthis cell death is 'necrotic'. This means that cell components escape,attract other immune cells and activating them. Ultimately the resultis inflammation and tissue damage. 'It is quite possible thatrhodococci do not really mind this,' Professor Haas says, 'since theycan then grab a passing macrophage and colonise fresh material.'
The next aim of the Bonn researchers is to investigate whichbacterial features are important for preventing the merger ofphagosomes and lysosomes, and how the immune system normallysuccessfully eradicates an infection despite all the tricks thebacteria use.
Rhodococci, incidentally, can also cause diseases resembling TBin AIDS patients which may be fatal. 'This is an additional importantaspect for our work,' Prof. Haas stresses. 'We assume that our researchcan contribute to understanding TB in humans.' Unlike foals, however,the vast majority of humans do not need to be afraid of this pathogen.'In every spadeful of soil from an affected farm there are millionsupon millions of rhodococci, yet it practically never happens thathealthy humans are successfully infected by them.'
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