Sensory neurons regulate stimulus-dependent humoral immunity in mouse models of bacterial infection and asthma.

Our immune system normally defends us from harmful invaders like bacteria and allergens. But our nerves—specifically, sensory neurons—also play a surprising role in this defense. A recent study in mice has uncovered how these nerves help the immune system produce antibodies, the proteins that recognize and neutralize threats. Sensory neurons are the nerves that detect sensations like pain, temperature, and touch. It is already known that they could sense infections and trigger quick immune responses. But this study asked a new question: do these nerves also help the body make antibodies, which are part of the longer-term immune defense? To find out, researchers studied two different models in mice: a bacterial lung infection caused by Streptococcus pneumoniae and an asthma-like condition triggered by a common allergen called Alternaria alternata. In both cases, they found that when sensory neurons were removed or disabled, the mice had weaker immune responses. They produced fewer B cells (the cells that make antibodies), and their levels of protective antibodies like IgG and IgE dropped. As a result, the mice had more severe infections or reduced asthma symptoms. Digging deeper, the scientists discovered that sensory neurons help by releasing special signaling molecules called neuropeptides. During bacterial infections, the nerves released a molecule called VIP (vasoactive intestinal polypeptide). VIP helped the immune system fight the infection by boosting antibody production and reducing the number of bacteria. When VIP was missing or its receptor (VIPR1) was blocked, the infection got worse. In contrast, during asthma, the nerves released a different molecule called substance P. This molecule made the allergic reaction stronger. When substance P was added to mice without sensory neurons, their asthma symptoms returned. But when substance P was blocked, the asthma symptoms improved. These findings show that sensory neurons don’t just detect danger—they also help shape how the immune system responds. Depending on the type of threat, they release different molecules that either boost or calm the immune response. This discovery opens exciting new possibilities for treating diseases. For example, boosting VIP might help people fight bacterial infections more effectively, while blocking substance P could ease asthma symptoms. In short, this research reveals a hidden partnership between the nervous system and the immune system. Our nerves are not just messengers of pain or itch—they are also key players in helping our bodies stay healthy.