Abstract

Vascular congestion and coagulopathy have been shown to play a role in human and experimental cerebral malaria (eCM), but little is known about the role of microglia, or microglia-vascular interactions and hypercoagulation during disease progression in this fatal infection. Recent studies show microglia bind to fibrinogen, a glycoprotein involved in thrombosis. An eCM model of Plasmodium chabaudi infection in mice deficient in the regulatory cytokine IL-10 manifests neuropathology, including hypercoagulation with extensive fibrin(ogen) deposition and neuroinflammation. Intravital microscopy and immunofluorescence are applied to elucidate the role of microglia in eCM. Results show microgliosis and coagulopathy occur early in disease at 3 dpi (day post-infection), and both are exacerbated as disease progresses to 7dpi. Vessel associated microglia increase significantly at 7 dpi, and the expression of the microglial chemoattractant CCL5 (RANTES) is increased versus uninfected and localized with fibrin(ogen) in vessels. PLX3397 microglia depletion resulted in rapid behavioral decline, severe hypothermia, and greater increase in vascular coagulopathy. This study suggests that microglia play a prominent role in controlling infection-initiated coagulopathy and supports a model in which microglia play a protective role in cerebral malaria by migrating to and patrolling the cerebral vasculature, potentially regulating degree of coagulation during systemic inflammation.

Details

Title
Dynamic intravital imaging reveals reactive vessel-associated microglia play a protective role in cerebral malaria coagulopathy
Author
Solomon, Olivia D. 1 ; Villarreal, Paula 1 ; Domingo, Nadia D. 2 ; Ochoa, Lorenzo 3 ; Vanegas, Difernando 4 ; Cardona, Sandra M. 4 ; Cardona, Astrid E. 4 ; Stephens, Robin 5 ; Vargas, Gracie 6 

 University of Texas Medical Branch, The Institute for Translational Sciences, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964); University of Texas Medical Branch, Biomedical Engineering and Imaging Sciences Group, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964); University of Texas Medical Branch, Department of Neurobiology, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
 Rutgers New Jersey Medical School, Center for Immunity and Inflammation, Newark, USA (GRID:grid.430387.b) (ISNI:0000 0004 1936 8796); University of Texas Medical Branch, Department of Internal Medicine, Division of Infectious Diseases, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
 University of Texas Medical Branch, Biomedical Engineering and Imaging Sciences Group, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964); University of Texas Medical Branch, Department of Neurobiology, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
 University of Texas at San Antonio, Department of Molecular Microbiology and Immunology, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633) 
 Rutgers New Jersey Medical School, Center for Immunity and Inflammation, Newark, USA (GRID:grid.430387.b) (ISNI:0000 0004 1936 8796); University of Texas Medical Branch, Department of Internal Medicine, Division of Infectious Diseases, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964); Rutgers New Jersey Medical School, Department of Pharmacology, Physiology and Neuroscience, Newark, USA (GRID:grid.430387.b) (ISNI:0000 0004 1936 8796); University of Texas Medical Branch, Department of Microbiology and Immunology, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
 University of Texas Medical Branch, Biomedical Engineering and Imaging Sciences Group, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964); University of Texas Medical Branch, Department of Internal Medicine, Division of Infectious Diseases, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
Pages
19526
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2887745330
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.