Sub-specialists

In recent years, immunologists have discovered that dendritic cells have sub-specialisations. Degli Esposti says MCMV infection activates at least two subsets of dendritic cells: conventional DCs as well as the recently identified plasmacytoid DCs.

It had been thought that plasmacytoid DC sounded the type 1 interferon alarm bells, but the Degli Esposti team showed that this function is not restricted to this DC subset.

Type I interferons are critical players in anti-viral immunity, as they not only have important direct anti-viral activities, but are also required for efficient activation of NK cell killing.

In a paper published in Nature Immunology in 2005, Degli-Esposti and colleagues showed that conventional DCs can secrete type I interferons in response to MCMV infection, and that this response is sufficient to activate NK cells.

"In showing that different subsets of dendritic cells can interact with NK cells in the very early phase of the immune response, we've discovered important new aspects of innate immunity."

While controlling pathogens is important, few viral infections are lethal in their own right - it makes no evolutionary sense for a virus to kill its host.

"It seems that it is much more detrimental to the host to be unable to switch off the immune response itself," she says.

"If the immune system cannot control activated effectors, it is a big problem and the pathology that ensues is often fatal. Activated effectors secrete a number of cytokines, including TNF-alpha and interferon gamma, which we have shown can cause very detrimental pathological effects.

"If the immune system can't turn off that response and avoid a massive cytokine storm, it can cause much more damage that being unable to control viral loads per se."

Some particularly virulent viruses, like the current H5N1 strain of avian influenza, trigger a deadly cytokine storm that can kill the host.

"The fact that most viruses do not directly kill their hosts makes perfect evolutionary sense. You must never compromise your ability to generate progeny and spread.

"For the host's part, it has to deal with the pathogen so it doesn't take over completely, but it's just as critical to ensure that immune responses are limited and can be switch off.

"We need to understand the balance between the host and the pathogen - how they 'talk' to each other and how the immune system is geared so that damaging responses, that can cause immunopathology, are controlled and limited."