title: mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis.
abstract: Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brooklyn Avenue, Boston, Massachusetts 02215, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Hallowell
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Collins
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 650 North Wolfe Street, Baltimore, Maryland 21205, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Craig
authors.affiliation: Department of Respiratory Diseases, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200433, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Oh
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Illei
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chan-Li
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Vigeland
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 650 North Wolfe Street, Baltimore, Maryland 21205, USA.
authors.forename: W
authors.initials: W
authors.lastname: Mitzner
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 650 North Wolfe Street, Baltimore, Maryland 21205, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Scott
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Powell
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 735 North Broadway, Baltimore, Maryland 21205, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Horton
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D006374:Helminthiasis, Animal / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus / Q000276:immunology; D000076226:Rapamycin-Insensitive Companion of mTOR Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D022722:Thermogenesis / Q000502:physiology*
chemical_list: D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C525637:rictor protein, mouse; D000076225:Mechanistic Target of Rapamycin Complex 2