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

Front. Immunol. | doi: 10.3389/fimmu.2019.02492

Memory-like inflammatory responses of microglia to rising doses of LPS: Key role of PI3Kγ

  • 1Institute of Molecular Cell Biology, University Hospital Jena, Germany
  • 2Department of Neonatology, Center of Pediatrics, Heidelberg University Hospital, Germany
  • 3Center of Excellence for Inflammation, Infectious Disease & Immunity, Quillen College of Medicine, East Tennessee State University, United States
  • 4Department of Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Germany
  • 5University Hospital Jena, Germany

Trained immunity and immune tolerance have been identified as long-term response patterns of the innate immune system. The causes of these opposing reactions remain elusive. Here we report about differential inflammatory responses of microglial cells derived from neonatal mouse brain to increasing doses of the endotoxin LPS. Prolonged priming with ultra-low LPS doses provokes trained immunity, i.e. increased production of pro-inflammatory mediators in comparison to the unprimed control. In contrast, priming with high doses of LPS induces immune tolerance implying decreased production of inflammatory mediators and pronounced release of anti-inflammatory cytokines. Investigation of the signaling processes and cell functions involved in these memory-like immune responses reveals essential role of phosphoinositide 3-kinase γ (PI3Kγ), one of the phosphoinositide 3-kinase species highly expressed in innate immune cells. Together, our data suggest profound influence of preceding contacts with pathogens on the immune response of microglia. The impact of these interactions – trained immunity or immune tolerance - appears to be shaped by pathogen dose.

Keywords: Microglia,, PI3Kγ signaling, LPS (lipopolysaccharide), β-Glucan, training, tolerance, Phagocytosis

Received: 31 May 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Lajqi, Lang, Haas, Williams, Hudalla, Bauer, Wetzker and Bauer. 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. Reinhard Bauer, University Hospital Jena, Jena, Germany, reinhard.bauer@med.uni-jena.de