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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02231

Mimicry of Central-Peripheral Immunity in Alzheimer’s Disease and Discovery of Neurodegenerative Roles in Neutrophil

  • 1Center for Biomedical Engineering and Science, Dep of Mechanical Engineering and Engineering Science, Dep of Biological Sciences, The Nanoscale Science Program, University of North Carolina at Charlotte, United States
  • 2Department of Biochemistry and Biomedical Sciences, Seoul National University Hospital, South Korea
  • 3Department of Surgery, Massachusetts General Hospital, Harvard Medical School, United States
  • 4Dep of Surgery, Massachusetts General Hospital, Harvard Medical School, United States
  • 5Institute of Quantum Biology, Sungkyunkwan University, South Korea

Neuroinflammatory roles of central innate immunity in brain parenchyma are well regarded in the progression of neurodegenerative disorders including Alzheimer’s disease (AD), however, the roles of peripheral immunity in central nervous system (CNS) diseases are less clear. Here, we created a microfluidic environment of human AD brains: microglial neuroinflammation induced by soluble amyloid-beta (Abeta), a signature molecule in AD and employed the environment to investigate the roles of neutrophils through the central-peripheral innate immunity crosstalk. We observed that soluble Abeta-activated human microglial cells produced chemoattractants for neutrophils including IL6, IL8, CCL2, CCL3/4, CCL5 and consequently induced reliable recruitment of human neutrophils. Particularly, we validated the discernable chemo-attractive roles of IL6, IL8, and CCL2 for neutrophils by interrupting the recruitment with neutralizing antibodies. Upon recruitment, neutrophils released inflammatory mediators such as MIF and IL2, detrimental to brain cells. We envision that targeting the crosstalk between central-peripheral immune community is a potential strategy to reduce immunological burdens in other neuroinflammatory CNS diseases.

Keywords: neuroinflamamation, Neurodegenaration, Microglia, Alzheheimer's disease, Neutrophil

Received: 24 Jun 2019; Accepted: 03 Sep 2019.

Copyright: © 2019 Park, Baik, Mook-Jung, Irimia and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Daniel Irimia, Massachusetts General Hospital, Harvard Medical School, Department of Surgery, Boston, 02114, Massachusetts, United States, daniel_irimia@hms.harvard.edu
Prof. Hansang Cho, University of North Carolina at Charlotte, Center for Biomedical Engineering and Science, Dep of Mechanical Engineering and Engineering Science, Dep of Biological Sciences, The Nanoscale Science Program, Charlotte, 28223, North Carolina, United States, h.cho@uncc.edu