The survival of living organisms depends on their capacity to mount a defense against environmental agents that cause tissue damage and infection. Traditionally, the activity of the immune system in repairing tissue injury and combating pathogens has been considered quite different from that of the nervous system, which transduces environmental or internal damaging signals into electrical activity to produce reflexes and sensations. However, anatomical and cellular bases for bidirectional interactions between these two systems have been established. Our laboratory investigates how neural and immune signals are interconnected and integrated to shape the host response to pathogens and injuries.


Stress can be defined as a state of altered homeostasis resulting from external or internal stimuli, including inflammatory processes, infections and pain. In response to these stimuli, various adaptive neuroendocrine mechanisms are induced to restore homeostasis. Part of this response is initiated within the central nervous system and translated into action by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system. These neuroendocrine pathways have been shown to modulate inflammatory and immune responses. In addition, sensory nerves are stimulated when an injury, an infection or an inflammation occurs in tissues. These neurons convey the damaging information to the brain (inducing pain) and release a number of mediators and neuropeptides in situ that can modulate the function of immune cells locally. A new paradigm in which the nervous system regulates immune functions is emerging. The goal of our lab is to identify new regulatory mechanisms affecting the immune response by investigating the functional role of the nervous system in immunity. Our research program has two main axes.

Role of neuroendocrine stimulation in innate immune responses

Following stress, infection or inflammation, stimulation of the HPA axis and the sympathetic nervous system (SNS) induces the adrenal gland to release epinephrine and glucocorticoids into the bloodstream. Nerve fibers from the SNS also release the neurotransmitter norepinephrine into lymphoid organs and tissues. These mediators can stimulate adrenergic receptors (AR) and glucocorticoid receptors (GR) on leukocytes. We are studying the role of these receptors in innate lymphoid cells (ILCs) and myeloid cells. We have already shown that host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 ILCs (Quatrini at al. 2017) revealing a novel strategy of host protection from immunopathology.

We are now analyzing the roles of these receptors in regulating immune cell functions in the contexts of viral infection and tumor development.

Role of sensory neurons and pain sensitivity in immunity

Nociceptors are primary sensory neurons that detect noxious stimuli and inform the brain of the occurrence of inflammatory processes. All tissues highly exposed to the external environment, such as the epithelial surfaces of the skin, are densely innervated by nociceptors. These sensory neurons can release many neuropeptides, and some can attract or activate innate immune cells (mast cells, DC) and T lymphocytes. The production of these neuropeptides by nociceptors may, thus, affect the first steps of the immune response, altering the efficacy of adaptive immune responses. Recent studies have shown that some skin pathogens can cause pain by directly activating nociceptors and suggested that sensory neurons may modulate inflammation.
Nociceptors were also implicated in skin inflammation in a mouse model of psoriasis. In these studies, opposite effects of nociceptors were reported: immunosuppressive effects upon infection with the bacterium Staphylococcus aureus and pro-inflammatory effects in models of chemically induced psoriasis and in Candida albicans infection. These recent findings show that nociceptive fibers can integrate environmental signals to modulate local immune responses. However, our understanding of these new pathways for regulating immune responses is extremely limited, and many unknowns remain. We are analyzing the role played by nociceptors in the activation and recruitment of immune cells in the skin after tissue damage, inflammation or infection, and in the generation of adaptive immune responses. In particular, we are using genetic mouse models in which the innervation of the skin by primary sensory neurons is either defective or completely abolished. These mice have impaired sensitivity to injury and inflammation-induced pain and are valuable tools for investigating the role of sensory nerves in the immune response in vivo.

Our studies should provide new insight into the mechanisms by which the nervous and immune systems cooperate to ensure a controlled and appropriate response to pathological challenges, to restore homeostasis.