Environmental perception and control of gastrointestinal immunity by the enteric nervous system

The enteric nervous system (ENS) is in its organization, structure, and function more similar to the central nervous system (CNS) than to other parts of the peripheral nervous system (PNS). Recent groundbreaking advances in single-cell genomics and imaging technologies allow unprecedented insights into different functional neuron and glia populations. Enteric neurons closely interact with glia cells and virtually all intestinal cell types. These interactions position the ENS in the center of manifold regulatory circuits for immunity and metabolism under homeostatic and pathophysiological conditions. Together, the ENS, enterocytes, and immune cells form one of the body’s most advanced sensory systems that is strategically located in the gastrointestinal wall to trigger orchestrated responses to environmental changes. The enteric nervous system (ENS) forms a versatile sensory system along the gastrointestinal tract that interacts with most cell types in the bowel. Herein, we portray host–environment interactions at the intestinal mucosal surface through the lens of the enteric nervous system. We describe local cellular interactions as well as long-range circuits between the enteric, central, and peripheral nervous systems. Additionally, we discuss recently discovered mechanisms by which enteric neurons and glia respond to biotic and abiotic environmental changes and how they regulate intestinal immunity and inflammation. The enteric nervous system emerges as an integrative sensory system with manifold immunoregulatory functions under both homeostatic and pathophysiological conditions. The enteric nervous system (ENS) forms a versatile sensory system along the gastrointestinal tract that interacts with most cell types in the bowel. Herein, we portray host–environment interactions at the intestinal mucosal surface through the lens of the enteric nervous system. We describe local cellular interactions as well as long-range circuits between the enteric, central, and peripheral nervous systems. Additionally, we discuss recently discovered mechanisms by which enteric neurons and glia respond to biotic and abiotic environmental changes and how they regulate intestinal immunity and inflammation. The enteric nervous system emerges as an integrative sensory system with manifold immunoregulatory functions under both homeostatic and pathophysiological conditions. the adaptive immune system facilitates the adaptive and specific immune response to invading pathogens. Prior presentation and antigen processing are necessary to mount a proper adaptive response, allowing the pathogen’s elimination via humoral and cellular immunity. a subtype of glia cells in the CNS; astrocytes have a star-shaped appearance and play various supportive functions to maintain CNS homeostasis. part of the PNS that forms complex circuits to control various vegetative parameters (temperature, digestion, secretion, cardiorespiratory function, and more) to maintain the internal body milieu. The ANS includes the mostly antagonistic sympathetic and parasympathetic branches and the ENS. neuronal circuits of the brain and spinal cord. dorsal root ganglia lie in the intervertebral foramina and contain collections of neuronal cell bodies of sensory neurons that relay sensory information from the periphery into the CNS. protects the body from foreign antigens and harmful pathogens. In contrast to the adaptive immune system, initiation of immunological response does not require prior antigen presentation and training. Still, the innate immune system depends on recognition of conserved patterns which are recognized by inborn defense systems. lymphoid cells that are highly abundant in mucosal barrier tissues such as the gut and constitute the innate counterparts of T cells. They orchestrate innate and adaptive immunity via various cytokines and chemokines. cells that serve as pacemakers in the gastrointestinal tract. ICCs generate slow waves that help to coordinate contractions of smooth muscle cells necessary for normal motility. unmyelinated sensory neurons located in the ENS. These neurons sense mechanical and chemical stimuli in coordination with enteroendocrine cells and form circuits with interneurons and motor neurons. These circuits allow the execution of complex gastrointestinal functions without CNS input. collections of bacteria that colonize different parts of the body. cells that are involved in mucosal immunity and transport of luminal molecules and microbial components across the epithelial cell layer. They are located adjacent to lymphoid tissue of the gut. branch of the autonomic nervous system that controls vegetative functions. Parasympathetic activation increases bowel motility, reduces bowel sphincter tone, and modulates the function of most internal organs. all peripheral nerves, glia, ganglia, and plexi. sequencing technology that allows transcriptomic profiling of whole tissues on the single-cell level. Neurons are large, which results in low efficiency of cell encapsulation in sequencing droplets. Isolation of nuclei solves this problem with gene detection comparable to scRNA sequencing. specialized types of muscle cell found in the wall of the bowel, bladder, vasculature, and airways. SMCs do not have sarcomeres like skeletal or cardiac muscle; they contract and relax slowly compared to skeletal muscle, and can generate tonic or phasic contractions over a wide range of dimensions. SMC are the bowel cells that generate force to prevent distension and support motility. a branch of the autonomic nervous system that controls vegetative functions. Sympathetic activation slows bowel motility, tightens bowel sphincters and modulates the function of most internal organs. evolutionarily highly conserved pathogen recognition receptors that are part of the innate immune system and detect specific molecular patterns (e.g., lipopolysaccharide, LTA) to initiate an immune response or regulate cell function. immune responses initiated to fight extracellular parasites and helminths. They help to maintain metabolic homeostasis and regulate tissue repair following injury.