Alongside the predictable physical effects of viral infections, like sore throat and fever, people often experience a drop in mood and cognitive ability. New research published in Immunity might have tracked down the molecular origins of this depressing feature of the flu.

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The molecules responsible for depression during infection might finally have been pinned down.

There are a wealth of studies describing how emotional states, such as anxiety and stress, can negatively impact the ability of the immune system to fight off invaders.

Conversely, there is a growing body of research measuring how the activity of the immune system is able to reduce psychological and cognitive functioning.

Although the interplay between immunity and psychology is now well documented, the precise ways in which the two systems interact are not understood.

Thomas Blank and Marco Prinz, of the University of Freiburg, Germany, set out to investigate how viral infections can induce depressive-like behavior, cognitive deficits and pervasive sleepiness.

Individuals who are attempting to ward off a viral infection naturally produce type I interferons, so-called because they interfere with the virus’ ability to replicate; these proteins coordinate immune reactions by recruiting and activating immune components.

Interferons are also used in the treatment of cancer, hepatitis C and multiple sclerosis; patients receiving them clinically are known to experience similar psychological symptoms and mood shifts to those seen in patients with viral infections.

It seems that type I interferons might be involved in the cognitive and emotional changes of viral infection, but the mechanisms by which these proteins might carry out the changes are a mystery. For this reason, Blank and colleagues decided to investigate the molecular machinations in more detail.

The researchers infected mice with vesicular stomatitis virus, which produces flu-like symptoms in humans. During tests, the infected mice displayed signs of despair, such as an increased duration in their “immobility response,” a well-known behavior, demonstrating that the viral load had induced depression-like symptoms as expected.

The team investigated the role of two specific cell types within the mice brains: brain endothelial cells, which line the interior surfaces of the brain’s blood vessels; and epithelial cells, which line the inside of the brain’s ventricles (fluid-filled spaces within the brain that produce cerebrospinal fluid).

The noted drop in mood was found to require the activation of a specific chemokine signaling pathway, called CXCL10/CXCR3. Chemokines are a subtype of cytokine and comprise around 50 distinct proteins; they act as attractants, by sending out chemical signals to orchestrate the movements of other cells. During the immune response, they play a part in directing the movements of immune components, such as lymphocytes.

In the current study, it was noted that CXCL10 was released from both endothelial and epithelial cells, and it then bound to CXCR3 receptors. This binding went on to impair and hinder functioning within the hippocampus, a section of the brain thought to play a considerable role in emotion and the creation of memories.

Blank explains:

We identified brain endothelial and epithelial cells […] as natural gate-keepers for virus-induced sickness behavior, and established a potential target for the treatment of behavioral changes during virus infection or type I interferon therapy.”

The results infer a role for the endothelial and epithelial cells as messengers between the immune system and central nervous system.

The team plans to continue their research into the molecular basis of the sickness response. The current results might be clinically useful in the future. Blank says, “our findings suggest that preventing the release of CXCL10, or blocking its receptors at an early phase, should eliminate at least the initial stages of sickness behavior seen in response to viral infection or type I interferon therapy.”

Although the study was carried out on mice and will, therefore, take time to trickle down to humans, the results could be the foundation of understanding these types of psychological deficits due to immune responses. The mystery behind the emotive and cognitive effects of the flu might finally be unwrapped.

Medical News Today recently covered research asking whether synthetic immune cells could be a possible solution to antibiotic resistance.