Abstract
Intestinal macrophages are strategically located in different layers of the intestine, including the mucosa, submucosa and muscularis externa, where they perform complex tasks to maintain intestinal homeostasis. As the gastrointestinal tract is continuously challenged by foreign antigens, macrophage activation should be tightly controlled to prevent chronic inflammation and tissue damage. Unraveling the precise cellular and molecular mechanisms underlying the tissue-specific control of macrophage activation is crucial to get more insight into intestinal immune regulation. Two recent reports provide unanticipated evidence that the enteric nervous system (ENS) acts as a critical regulator of macrophage function in the myenteric plexus. Both studies clearly illustrate that enteric neurons reciprocally interact with intestinal macrophages and are actively involved in shaping their phenotype. This concept has striking parallels with the central nervous system (CNS), where neuronal signals maintain microglia, the resident macrophages of the CNS, in a quiescent, anti-inflammatory state. This inevitably evokes the perception that the ENS and CNS share mechanisms of neuroimmune interaction. In line, intestinal macrophages, both in the muscularis externa and (sub)mucosa, express high levels of CX3CR1, a feature that was once believed to be unique for microglia. CX3CR1 is the sole receptor of fractalkine (CX3CL1), a factor mainly produced by neurons in the CNS to facilitate neuron-microglia communication. The striking parallels between resident macrophages of the brain and intestine might provide a promising new line of thought to get more insight into cellular and molecular mechanisms controlling macrophage activation in the gut.
Highlights
This concept has striking parallels with the central nervous system (CNS), where neuronal signals maintain microglia, the resident macrophages of the CNS, in a quiescent, anti-inflammatory state
Laboratory of Neuroimmune Interaction and Mucosal Immunology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
The intimate crosstalk between enteric neurons and intestinal macrophages generates new perspectives on the cellular and molecular players involved in neuroimmune interaction in the gut. These findings suggest that neuroimmune crosstalk in the enteric nervous system (ENS) and central nervous system (CNS) occurs through equivalent modes-of-action
Summary
This concept has striking parallels with the central nervous system (CNS), where neuronal signals maintain microglia, the resident macrophages of the CNS, in a quiescent, anti-inflammatory state. Intestinal macrophages, both in the muscularis externa and (sub)mucosa, express high levels of CX3CR1, a feature that was once believed to be unique for microglia. Neural control of intestinal macrophages improved functional outcome mainly through the reduction of muscular inflammation, an effect mediated by activation of cholinergic enteric neurons in close contact with resident macrophages of the myenteric plexus.
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