Abstract：
:Enteric-associated neurons (EANs) are closely associated with immune cells and continuously monitor and modulate homeostatic intestinal functions, including motility and nutrient sensing. Bidirectional interactions between neuronal and immune cells are altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated the effects of infection-induced inflammation on intrinsic EANs (iEANs) and the role of intestinal muscularis macrophages (MMs) in this context. Using murine models of enteric infections, we observed long-term gastrointestinal symptoms, including reduced motility and loss of excitatory iEANs, which was mediated by a Nlrp6- and Casp11-dependent mechanism, depended on infection history, and could be reversed by manipulation of the microbiota. MMs responded to luminal infection by upregulating a neuroprotective program via β2-adrenergic receptor (β2-AR) signaling and mediated neuronal protection through an arginase 1-polyamine axis. Our results identify a mechanism of neuronal death post-infection and point to a role for tissue-resident MMs in limiting neuronal damage.
journal_name
Celljournal_title
Cellauthors
Matheis F,Muller PA,Graves CL,Gabanyi I,Kerner ZJ,Costa-Borges D,Ahrends T,Rosenstiel P,Mucida Ddoi
10.1016/j.cell.2019.12.002subject
Has Abstractpub_date
2020-01-09 00:00:00pages
64-78.e16issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(19)31328-5journal_volume
180pub_type
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