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Front. Psychiatry | doi: 10.3389/fpsyt.2018.00060

Sterile inflammation of brain, due to activation of innate immunity, as a culprit in psychiatric disorders

 Mariusz Z. Ratajczak1, 2*, Daniel Pedziwiatr2, Monika Cymer2, Magda Kucia1, 2,  Jolanta Kucharska-Mazur3 and  Jerzy Samochowiec3
  • 1University of Louisville Physicians, United States
  • 2Regenerative Medicine, Medical University of Warsaw, Poland
  • 3Pomeranian Medical University, Poland

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review we will present the hypothesis that prolonged or chronic activation of the complement cascade directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the complement cascade (ComC) we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors (PRRs), including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into peripheral blood from bone marrow that are potentially involved in repair mechanisms.

Keywords: Sterile Inflammation, complement cascade, MBL, HO-1, Stem cell mobilization

Received: 06 Dec 2017; Accepted: 12 Feb 2018.

Edited by:

FERNANDO RODRIGUEZ DE FONSECA, Instituto de Investigación Biomédica de Málaga, Spain

Reviewed by:

Florence P. Varodayan, The Scripps Research Institute, United States
Henning Ulrich, University of São Paulo, Brazil
Joanna Hauser, Poznan University of Medical Sciences, Poland  

Copyright: © 2018 Ratajczak, Pedziwiatr, Cymer, Kucia, Kucharska-Mazur and Samochowiec. 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 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. Mariusz Z. Ratajczak, University of Louisville Physicians, Louisville, United States, mzrata01@louisville.edu