title: An atypical role for the myeloid receptor Mincle in central nervous system injury.
abstract: The C-type lectin Mincle is implicated in innate immune responses to sterile inflammation, but its contribution to associated pathologies is not well understood. Herein, we show that Mincle exacerbates neuronal loss following ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a model of transient middle cerebral artery occlusion but did not alter outcomes following heart or gut ischemia. High functional scores in Mincle KO animals using the focal cerebral ischemia model were accompanied by reduced lesion size, fewer infiltrating leukocytes and less neutrophil-derived cytokine production than isogenic controls. Bone marrow chimera experiments revealed that the presence of Mincle in the central nervous system, rather than recruited immune cells, was the critical regulator of a poor outcome following transient middle cerebral artery occlusion. There was no evidence for a direct role for Mincle in microglia or neural activation, but expression in a subset of macrophages resident in the perivascular niche provided new clues on Mincle's role in ischemic stroke.
authors: 1 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|2 School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
authors: Thiruma V
authors: TV
authors: Arumugam
authors: 2 School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.|3 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
authors: Silvia
authors: S
authors: Manzanero
authors: 4 Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia.|5 The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Milena
authors: M
authors: Furtado
authors: 2 School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
authors: Patrick J
authors: PJ
authors: Biggins
authors: 1 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Yu-Hsuan
authors: YH
authors: Hsieh
authors: 6 Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Mathias
authors: M
authors: Gelderblom
authors: 7 Queensland Institute for Medical Research, Herston, Brisbane, Australia.
authors: Kelli Pa
authors: KP
authors: MacDonald
authors: 4 Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia.
authors: Ekaterina
authors: E
authors: Salimova
authors: 8 Department of Pathology and Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yu-I
authors: YI
authors: Li
authors: 3 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
authors: Othmar
authors: O
authors: Korn
authors: 9 Institute of Neuroscience & Psychology, Wellcome Surgical Institute, University of Glasgow, Glasgow, UK.
authors: Deborah
authors: D
authors: Dewar
authors: 9 Institute of Neuroscience & Psychology, Wellcome Surgical Institute, University of Glasgow, Glasgow, UK.
authors: I Mhairi
authors: IM
authors: Macrae
authors: 10 School of Dentistry, The University of Queensland, Brisbane, Australia.
authors: Robert B
authors: RB
authors: Ashman
authors: 8 Department of Pathology and Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|11 Department of Neurology, Stroke Center, National Taiwan University Hospital, Taipei, Taiwan.
authors: Sung-Chun
authors: SC
authors: Tang
authors: 4 Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia.|5 The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Nadia A
authors: NA
authors: Rosenthal
authors: 2 School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.|12 Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
authors: Marc J
authors: MJ
authors: Ruitenberg
authors: 6 Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Tim
authors: T
authors: Magnus
authors: 3 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.|13 Faculty of Medicine, Department of Anatomy and Neuroscience, The University of Melbourne, Australia.
authors: Christine A
authors: CA
authors: Wells
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D007422:Intestines / Q000098:blood supply; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins
keywords: C-type lectin; ischemia; microglia; middle cerebral artery occlusion; sterile inflammation