Scientists Uncover New Role for Neurotransmitter That Helps Fight Infection

Scientists have shed new light on the complexities of the immune system that could help develop vaccines to boost natural defences against disease.

The body has two types of immune response which work together: an innate response, which is the body’s immediate way of tackling infections, and an adaptive response.

The adaptive immune system is developed largely to combat secondary infections: having recognised an invading pathogen it will produce antibodies that can attack the infection. Other responses can also be triggered, such as mucus production to trap and expel pathogens.

Researchers at Imperial College London have shown that one particular type of neurotransmitter, or signalling molecule, has an important role in our adaptive immune response as well as in the innate immune system. If this signalling molecule could be mimicked and incorporated into a drug formulation, it could potentially be used to boost people’s immunity to infection.The neurotransmitter, called acetylcholine, has a number of complex roles within the body. It helps to carry messages around the body’s nervous system to activate muscles, for example, while in the brain it is responsible for transmitting sensory information.

Acetylcholine is already known to also play a role in regulating the body’s innate immune response – for example, it can slow the inflammatory response to infection which, if unchecked, can lead to inflammatory diseases or organ damage.

In a study published in the journal PLOS Pathogens, a team from Imperial College London and the University of Cape Town showed that acetylcholine was also important for the production of cytokines – proteins which stimulate the body’s adaptive immune responses.

“We started to look at these neurotransmitters in relation to the adaptive immune response because of work that we had been doing on helminth parasites,” explained Professor Murray Selkirk, Head of the Department of Life Sciences at Imperial College London. “These parasitic worms have sophisticated ways of suppressing the immune system of their host. They release an enzyme that degrades acetylcholine. We suspected that this must be benefitting them in some way, suggesting that the neurotransmitter is doing something which is detrimental to the parasite.”

This image represents a neuron.
Researchers showed acetylcholine is important for the production of cytokines. Image adapted from the Imperial College London press release.

In a collaboration with scientists at the University of Cape Town, the team studied a group of mice bred to be unresponsive to acetylcholine acting on a specific receptor. Some of the mice were infected with helminth parasites and some with salmonella bacteria, and their adaptive immune responses were measured. They discovered that the mice were less able to fight off either infection effectively, indicating that the neurotransmitter had a role to play in adaptive immunity.

“We already knew that this neurotransmitter played an important role in the innate immune system, but what we have found in this study is that it also activates other responses that are important for adaptive immunity,” says Professor Selkirk. “We hope this finding could lead to new ways of boosting people’s ability to fight off infection.”

The results are also significant for the use of existing drugs such as Tiotropium, which is used to treat chronic obstructive pulmonary disease, and recently approved for treatment of asthma. These drugs work by inhibiting the neurotransmitter’s signalling system to impede smooth muscle contraction and mucus production – both of which worsen the symptoms of these diseases. This study suggests that in suppressing these, there could also be an effect on other immune responses, which now need to be investigated.

About this neuropsychiatry research

Study results appeared online Feb. 10 in Biological Psychiatry. Paola A. Spadaro, Charlotte R. Flavell, Jocelyn Widagdo, Vikram S. Ratnu, Michael Troup and Chikako Ragan with the University of Queensland, and John S. Mattick with the Garvan Institute of Medical Research contributed to the study, which was supported by the National Health & Medical Research Council of Australia, the Australian Research Council and the U.S. National Institute of Mental Health (grant 1R21MH103812).

Contact: Laura Gallagher – Imperial College London
Source: Imperial College London press release
Image Source: The image is adapted from the Imperial College London press release
Original Research: Full open access research for “The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection” by Matthew Darby, Corinna Schnoeller, Alykhan Vira, Fiona Culley, Saeeda Bobat, Erin Logan, Frank Kirstein, Jürgen Wess, Adam F. Cunningham, Frank Brombacher, Murray E. Selkirk, and William G. C. Horsnell in PLOS Pathogens. Published online January 28 2015 doi:10.1371/journal.ppat.1004636

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