Every smell you take – Smell-induced conditioning of the immune system during infections

forthcoming

The nervous and immune systems are the body’s primary sensory interfaces, perceiving and responding to environmental stimuli. Both systems can recall past challenges, enabling them to mount responses that anticipate and adapt to ever-changing situation. Recent research indicates that the brain can recall past infections, forming a new axis between neurological memory and immune response. A notable example of such interaction is Pavlovian or classical conditioning, where organisms learn the timing and causal relationships between internal and external stimuli, enabling them to prepare responses before significant events even occur. Importantly, pioneering studies have shown that the immune system can also be conditioned. However, it is still unclear whether conditioning can be used to boost immune response upon pathogen reencounter or during revaccinations. Furthermore, the fundamental neuroimmune mechanisms that promote conditioning remain largely unexplored. Although Pavlov initially used a bell to condition dogs, other stimuli, e.g. smells, can be even more effective due to their strong connection to memory and emotion. For example, the scent of freshly baked cookies can evoke vivid childhood memories. So, could the application of smell during a viral infection or vaccination trigger a stronger secondary immune response? Therefore, we hypothesize that an olfactory stimulus received during a primary infection or vaccination enhances the immune response after subsequent encounters. Thus, we propose combining advanced immunological and neuroscience techniques to understand how multiorgan, neuro-immune circuits regulate the immune response after conditioning with odor. Furthermore, we will investigate whether activating these circuits can inhibit pathogen replication, considering the limitations of current antiviral drugs and raising antibiotic resistance, with the goal of revolutionizing infectious disease prevention and boosting the effectiveness of vaccinations.