Neural and immune drivers of disease in tuberculosis, cancer, and tissue health
Michael Shiloh
University of Texas Southwestern Medical Center, Dallas, TX, The United States _
Mycobacterium tuberculosis
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nociceptive molecules activate lung innervating neurons and induce cough
------------------------------------------------------------------------------------------------------------- Cough is a vital respiratory reflex orchestrated by lung innervating nociceptive or pain-sensing neurons to clear the airways of noxious material. Although cough is protective, it can also be exploited by pathogens to facilitate aerosol transmission and is a hallmark symptom of active TB disease. Bacterial pathogens are known to interact directly and indirectly with nociceptive neurons, however the mechanisms by which Mtb interacts with sensory neurons remain largely uncharacterized. Our previous work identified a glycolipid, sulfolipid-1, that is produced by Mtb that directly activates cough-inducing nociceptive neurons. Additionally, using whole body plethysmography of guinea pigs, we found that sulfolipid-1 is necessary and sufficient to trigger a cough reflex. Due to the heterogeneity of cell wall lipids produced by Mtb strains, we hypothesized that clinical hypervirulent strains may produce additional nociceptive molecules. We have identified a molecule unique to a hypervirulent Mtb strain (HN878) that activates both mouse and human nociceptive neurons and induces cough in experimental animals. These results identify an additional mechanism for activation of cough inducing neurons by a hypervirulent Mtb strain. The unique and shared roles of Mtb cough-inducing molecules and their role in transmission will be discussed.
Sophie Chauvet
Aix Marseille Univ, CNRS, IBDM, Marseille, France
Unlocking the neural code: How Schwann cells drive tumor-associated nerve plasticity
---------------------------------------------------------------------------------------- The field of neuro-oncology focuses on the complex interaction between neurons and tumors. The peripheral nervous system (PNS), which connects the central nervous system to the body's organs, plays a key role in regulating physiological functions and is also a component of the tumor microenvironment, influencing tumor development. While nerves often promote tumor growth, the sympathetic nervous system has been shown to have a protective function in certain cancers, such as pancreatic ductal adenocarcinoma (PDAC). This presentation explores the role of Schwann cells (SCs) in the structural plasticity of neurons during tumor development. SCs are known for their adaptability, reprogramming to provide growth and guidance signals under adverse conditions. The study investigates changes in SC density, distribution, and morphology in the context of PDAC and chronic inflammation, and examines the contribution of these cells to sympathetic axon sprouting through neurotrophic signaling pathways. This research sheds light on the dynamic relationship between the nervous system and cancer, with implications for potential therapeutic strategies targeting neural remodeling.
Julie Ribot
Insituto de Medicina Molecular, Lisboa, Portugal
γδ T cells in tissue pathophysiology
---------------------------------------- γδ T cells are a unique T cell subpopulation that are rare in secondary lymphoid organs but enriched in many peripheral tissues, such as the skin, intestines and lungs. By rapidly producing large amounts of cytokines, γδ T cells make key contributions to immune responses in these tissues. In addition to their immune surveillance activities, recent reports have unraveled exciting new roles for γδ T cells in steady-state tissue physiology, with functions ranging from the regulation of thermogenesis in adipose tissue to the control of neuronal synaptic plasticity in the central nervous system. This seminar will present our recent work on the roles of γδ T cells in tissue homeostasis, as well as the homeostasis of γδ T cells in tissues.
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