Our goal is to understand the role of neuro-immune interactions in host defense and inflammation. The peripheral nervous system densely innervates barrier tissues including the skin, the gastrointestinal tract, and respiratory tract. Pain and stress affect the immune response against pathogens, but the underlying molecular and cellular mechanisms are not well understood. We have found that peripheral sensory neurons sense microbes to produce pain, and regulate the immune response during inflammation.
Neural-immune interactions in host defense and immunity
It is increasingly clear that the nervous system plays a powerful role in regulating the immune system during inflammation. We recently found that sensory neurons play a key role in regulating bacterial host defense. Sensory neurons release neuropeptides (e.g. CGRP, SP, or VIP) which act on their cognate receptors on immune cells to modulate immune function. Sympathetic neurons release norepinephrine which acts on adrenergic receptors expressed by immune cells. We are now investigating the role of these neuro-immune interactions in the skin, gut, and respiratory tract. We aim to use targeted genetic and pharmacological tools to ascertain the role of these neuro-immune interactions in host defense against pathogens and in tissue inflammation.
Neuronal sensing of bacteria in pain and infection
Pain is a component of many infectious diseases, including bacterial and viral infection. We have found that nociceptor sensory neurons are directly activated by bacterial pathogens and their secreted factors produce pain. We have found that different types of gut-commensal microbes are able to directly induce calcium influx in DRG sensory neurons. The gut-brain-axis could be involved in regulating pain. We are identifying the key molecular mechanisms by which different types of microbes and pathogens induce neuronal activation. Isolation of microbe-derived neuromodulatory factors could lead to new treatments for chronic pain and infectious diseases.
Neural-immune cross-talk in inflammation
Nociceptors and pruriceptors are the specific subsets of sensory neurons that produce pain and itch, respectively. However, the mechanisms leading to chronic pain or itch are not well understood. Atopic dermatitis is a skin disease characterized by chronic itch. Chronic neuropathic pain is a widespread condition where there are few effective treatments. Sensory neurons express receptors for specific immune derived factors, including interleukins and lipid mediators. We are investigating how specific immune signaling mechanisms may drive chronic itch or chronic pain. We are also investigating if neurons play a role in driving inflammatory diseases at barrier tissues such as the GI tract, respiratory tract, and skin.
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