An atypical role for the myeloid receptor Mincle in central nervous system injury

Thiruma V Arumugam, Silvia Manzanero, Milena Furtado, Patrick J. Biggins, Yu Hsuan Hsieh, Mathias Gelderblom, Kelli P A MacDonald, Ekaterina Salimova, Yu I. Li, Othmar Korn, Deborah Dewar, I. Mhairi Macrae, Robert B Ashman, Sung-Chun Tang, Nadia A. Rosenthal, Marc J Ruitenberg, Tim Magnus, Christine A Wells

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)2098-2111
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • C-type lectin
  • Ischemia
  • Microglia
  • Middle cerebral artery occlusion
  • Sterile inflammation

Cite this

Arumugam, T. V., Manzanero, S., Furtado, M., Biggins, P. J., Hsieh, Y. H., Gelderblom, M., ... Wells, C. A. (2017). An atypical role for the myeloid receptor Mincle in central nervous system injury. Journal of Cerebral Blood Flow and Metabolism, 37(6), 2098-2111. https://doi.org/10.1177/0271678X16661201
Arumugam, Thiruma V ; Manzanero, Silvia ; Furtado, Milena ; Biggins, Patrick J. ; Hsieh, Yu Hsuan ; Gelderblom, Mathias ; MacDonald, Kelli P A ; Salimova, Ekaterina ; Li, Yu I. ; Korn, Othmar ; Dewar, Deborah ; Macrae, I. Mhairi ; Ashman, Robert B ; Tang, Sung-Chun ; Rosenthal, Nadia A. ; Ruitenberg, Marc J ; Magnus, Tim ; Wells, Christine A. / An atypical role for the myeloid receptor Mincle in central nervous system injury. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 6. pp. 2098-2111.
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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.",
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Arumugam, TV, Manzanero, S, Furtado, M, Biggins, PJ, Hsieh, YH, Gelderblom, M, MacDonald, KPA, Salimova, E, Li, YI, Korn, O, Dewar, D, Macrae, IM, Ashman, RB, Tang, S-C, Rosenthal, NA, Ruitenberg, MJ, Magnus, T & Wells, CA 2017, 'An atypical role for the myeloid receptor Mincle in central nervous system injury' Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 6, pp. 2098-2111. https://doi.org/10.1177/0271678X16661201

An atypical role for the myeloid receptor Mincle in central nervous system injury. / Arumugam, Thiruma V; Manzanero, Silvia; Furtado, Milena; Biggins, Patrick J.; Hsieh, Yu Hsuan; Gelderblom, Mathias; MacDonald, Kelli P A; Salimova, Ekaterina; Li, Yu I.; Korn, Othmar; Dewar, Deborah; Macrae, I. Mhairi; Ashman, Robert B; Tang, Sung-Chun; Rosenthal, Nadia A.; Ruitenberg, Marc J; Magnus, Tim; Wells, Christine A.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 6, 01.06.2017, p. 2098-2111.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - An atypical role for the myeloid receptor Mincle in central nervous system injury

AU - Arumugam, Thiruma V

AU - Manzanero, Silvia

AU - Furtado, Milena

AU - Biggins, Patrick J.

AU - Hsieh, Yu Hsuan

AU - Gelderblom, Mathias

AU - MacDonald, Kelli P A

AU - Salimova, Ekaterina

AU - Li, Yu I.

AU - Korn, Othmar

AU - Dewar, Deborah

AU - Macrae, I. Mhairi

AU - Ashman, Robert B

AU - Tang, Sung-Chun

AU - Rosenthal, Nadia A.

AU - Ruitenberg, Marc J

AU - Magnus, Tim

AU - Wells, Christine A

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N2 - 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.

AB - 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.

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KW - Ischemia

KW - Microglia

KW - Middle cerebral artery occlusion

KW - Sterile inflammation

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M3 - Article

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