S100A8/A9 Drives Neuroinflammatory Priming and Protects against Anxiety-like Behavior after Sepsis
- 1 May 2018
- journal article
- research article
- Published by The American Association of Immunologists in Journal Of Immunology
- Vol. 200 (9), 3188-3200
- https://doi.org/10.4049/jimmunol.1700834
Abstract
Sepsis commonly results in acute and chronic brain dysfunction, which dramatically increases the morbidity associated with this common disease. Chronic brain dysfunction in animal models of sepsis survival is linked to persistent neuroinflammation and expression of multiple cytokines. However, we have found previously that microglia predominantly upregulate the damage associated molecule S100A8/A9 after sepsis. In this article, we show that S100A8/A9 is increased in the brains of patients who died of sepsis and that S100A8 is expressed in astrocytes and myeloid cells. Using a mouse model of sepsis survival, we show that S100A8/A9 is persistently expressed in the brain after sepsis. S100A9 expression is necessary for recruitment of neutrophils to the brain and for priming production of reactive oxygen species and TNF-alpha secretion in microglia and macrophages. However, despite improving these indices of chronic inflammation, S100A9 deficiency results in worsened anxiety-like behavior 2 wk after sepsis. Taken together, these results indicate that S100A8/A9 contributes to several facets of neuroinflammation in sepsis survivor mice, including granulocyte recruitment and priming of microglial-reactive oxygen species and cytokine production, and that these processes may be protective against anxiety behavior in sepsis survivors.Keywords
This publication has 75 references indexed in Scilit:
- S100A8 and S100A9 Induce Cytokine Expression and Regulate the NLRP3 Inflammasome via ROS-Dependent Activation of NF-κB1PLOS ONE, 2013
- Myeloid-Related Protein-14 Contributes to Protective Immunity in Gram-Negative Pneumonia Derived SepsisPLoS Pathogens, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Long-term impact of systemic bacterial infection on the cerebral vasculature and microgliaJournal of Neuroinflammation, 2012
- UPS 2.0: unique probe selector for probe design and oligonucleotide microarrays at the pangenomic/ genomic levelBMC Genomics, 2010
- Selective Chemokine Receptor Usage by Central Nervous System Myeloid Cells in CCR2-Red Fluorescent Protein Knock-In MicePLOS ONE, 2010
- A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis*Critical Care Medicine, 2010
- INDUCTION OF ENDOTOXIN TOLERANCE ENHANCES BACTERIAL CLEARANCE AND SURVIVAL IN MURINE POLYMICROBIAL SEPSISShock, 2008
- Sepsis-induced suppression of lung innate immunity is mediated by IRAK-MJCI Insight, 2006
- Characterization of canine microglial cells isolated ex vivoVeterinary Immunology and Immunopathology, 2004