Our ability to appreciate a rose’s perfume, savor a plate of pasta or even feel pain after being stung by a bee depends on sensory nerves: bundles of neurons that project from the spinal cord into organs such as the skin, tongue and nose. At these organs, nerves detect stimuli coming from the external environment and transmit the information to the brain. However, sensory nerves are also found in organs that aren’t exposed to the external environment, such as the spleen and lymph nodes. These organs primarily play a role in housing immune cells to detect pathogens and initiate a response to effectively eliminate them. Because sensory nerves are surprisingly found in these organs, it is possible that, in addition to conveying external information to our brain, sensory nerves might also coordinate immune reactions against foreign invaders.

Researchers at the National Center of Biomedical Analysis went on to test this. They showed that sensory neurons in mice injected with influenza virus can detect the accumulation of splenic prostaglandin E (PGE2), a pro-inflammatory molecule, in the spleen and results in the release of a small neural protein called calcitonin gene-related peptide (CGRP). To test if this was required for viral clearance, they used a mice model where they could selectively eliminate all sensory neurons in the spleen. When infected with the influenza virus, these mice could not clear the pathogen as the spleen failed to produce a key molecule for viral neutralization: antibodies. However, sensory neuron deficient mice re-established the capacity to clear influenza virus when CGRP was injected by re-establishing antibody production.

Hence, this work introduces the possibility that enhancing sensory nerve function might improve the immune response towards pathogens. This is especially relevant for elderly individuals who are more susceptible to infections and display loss of sensory innervation across many organs. Finding strategies to promote sensory nerve health might make vaccinations more effective in the elderly and ensure they become less sick when infected with common viruses such as influenza.

The study was performed at the National Center of Biomedical Analysis and Tsinghua University by Min Wu, Guangping Song, Jianing Li, and Zengqing Song. 

Managing Correspondent: Allegra Carlotta Scarpa

Research Article: Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity (Cell)

Press Article: Nociceptors enhance humoral immunity (Nature)

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