Animal nervous systems regulate immune responses throughout the entire body, and do so at speeds phenomenally faster than those prompted by immunity-boosting interventions such as immunisation.
A team led by Henrique Veiga-Fernandes investigated the function of a type of immune cell known as ILC2. The acronym stands for “innate lymphoid cell” and denotes a family of lymphocytes – white cells – that were only discovered in 2010.
While the roles of various ILCs are still being interrogated, it has been established that they play important parts in the regulation of metabolic equilibrium – homeostasis – and inflammation. Deficiencies in ILC function have been linked to allergies and poor immune system responses.
One of the key functions of ILCs is their ability to communicate with peripheral nerve cells, and thus with the central nervous system and brain. In 2016 Veiga-Fernandes and colleagues published a study into another type of innate lymphoid cells – ILC3s – that are prevalent in the lining of the gut.
The researchers demonstrated that by receiving signals from neuron satellites called glia ILC3s were stimulated to produce compounds to fight bacterial infection. The study also found that blocking ILC3 function resulted in “a pronounced propensity towards gut inflammation and infection”.
A key property of ILCs is that they are not acquired during an organism’s life, but are present from birth. They are also strongly conserved, and have been found in evolutionarily ancient organisms such as lampreys.
In their latest research Veiga-Fernandes and his team examined the function of ILC2s, which are very common at barrier sites within the body – such as the gut, lungs and skin – and produce compounds that fight against parasitic infection.
The scientists found that the bug-fighting abilities of the cells was entirely dependent on a “dialogue” with peripheral nerve cells, dispelling previous ideas that the immune system operated autonomously.
“Nobody could have imagined that the nervous system coordinates, commands and controls the immune response throughout the whole organism,” says Veiga-Fernandes.
Furthermore, the immune response generated by the neuron-ILC2 interaction is lightning fast, prompting comparisons to the speed at which adrenaline produces responses in the nervous system.
“It’s one of the fastest and most powerful immune reactions we have ever seen,” continues Veiga-Fernandes.
ILC2 cells contain receptors for a neural messenger molecule called neuromedin U (NMU). As NMU is only produced by nerve cells, its presence was proof that the two cells types have a dedicated communications link.
To further test the hypothesis, however, Veiga-Fernandes and his team established two cohorts of mice – one standard, and the other engineered to have no ILC2 cells – and infected both with a common rodent hookworm.
The standard group successfully fought off the parasite, while the modified mob succumbed to inflammation and internal bleeding.
Interrogating the results, the researchers established that the peripheral nerve cells rapidly detected compounds secreted by the hookworms, and immediately began producing NMU. This, in turn, prompted a powerful immune response from the ILC2 cells.
The immune defence was activated within minutes of the infection being detected – compared to the days it takes the immune system to respond to weakened antigens in vaccines.
Whether the neuron-ILC2 relationship is the same in humans as it is in rodents remains to be discovered, as are any possible clinical implications.
“In humans, ILC2s also have NMU receptors,” says Veiga-Fernandes. “But we are still very far from understanding how we could safely use this neuro-immunological ‘bomb’; for now, we are at the fundamental research level.”