title: Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
abstract: Proper adaptation to environmental perturbations is essential for tissue homeostasis. In the intestine, diverse environmental cues can be sensed by immune cells, which must balance resistance to microorganisms with tolerance, avoiding excess tissue damage. By applying imaging and transcriptional profiling tools, we interrogated how distinct microenvironments in the gut regulate resident macrophages. We discovered that macrophages exhibit a high degree of gene-expression specialization dependent on their proximity to the gut lumen. Lamina propria macrophages (LpMs) preferentially expressed a pro-inflammatory phenotype when compared to muscularis macrophages (MMs), which displayed a tissue-protective phenotype. Upon luminal bacterial infection, MMs further enhanced tissue-protective programs, and this was attributed to swift activation of extrinsic sympathetic neurons innervating the gut muscularis and norepinephrine signaling to β2 adrenergic receptors on MMs. Our results reveal unique intra-tissue macrophage specialization and identify neuro-immune communication between enteric neurons and macrophages that induces rapid tissue-protective responses to distal perturbations.
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Department of Pathology, School of Veterinary Medicine, Avenue Prof. Orlando Marques de Paiva 87, Cidade Universitária, University of São Paulo, 05508 270 São Paulo, Brazil.
authors.forename: Ilana
authors.initials: I
authors.lastname: Gabanyi
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Muller
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Feighery
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Department of Pathology, School of Veterinary Medicine, Avenue Prof. Orlando Marques de Paiva 87, Cidade Universitária, University of São Paulo, 05508 270 São Paulo, Brazil.
authors.forename: Frederico A
authors.initials: FA
authors.lastname: Costa-Pinto
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: mucida@rockefeller.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
mesh_terms: D000818:Animals; D002460:Cell Line; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000502:physiology; D015213:Neuroimmunomodulation; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000502:physiology; D013047:Specific Pathogen-Free Organisms
chemical_list: D018343:Receptors, Adrenergic, beta-2