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

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00154

Immune-modulatory effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide in acute Toxoplasmosis

  • 1Medizinische Fakultät, Universitätsklinikum Magdeburg, Germany
  • 2Institute of Psychology, Faculty of Life Sciences, Humboldt University Berlin, Germany
  • 3University of Veterinary Medicine Budapest, Hungary
  • 4Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Hungary
  • 5Department of Anatomy, Medical School, University of Pécs, Hungary
  • 6Charité Centrum Innere Medizin und Dermatologie, Charité Universitätsmedizin Berlin, Germany

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is an endogenous neuropeptide with distinct functions including the regulation of inflammatory processes. PACAP is able to modify the immune response by directly acting on macrophages and monocytes inhibiting the production of inflammatory cytokines, chemokines and free radicals. Here, we analyzed the effect of exogenous PACAP on peritoneal immune cell subsets upon acute infection with the parasite Toxoplasma gondii (T. gondii). PACAP administration was followed by diminished innate immune cell recruitment to the peritoneal cavity of T. gondii-infected mice. PACAP did not directly interfered with parasite replication, instead, indirectly reduced parasite burden in mononuclear cell populations by enhancing their phagocytic capacity. Although, proinflammatory cytokine levels were attenuated in the periphery upon PACAP administration, IL-10 and TGF-beta remained stable. While PACAP modulated VPAC1 and VPAC2 receptors in peritoneal immune cells upon binding, it also increased their expression of brain-derived neurotrophic factor (BDNF). In addition, the expression of p75 neurotrophin receptor (p75NTR) on Ly6Chi inflammatory monocytes was diminished upon PACAP administration. Our findings highlight the immunomodulatory effect of PACAP on peripheral immune cell subsets during acute Toxoplasmosis, providing new insights about host-pathogen interaction and the effects of neuropeptides during inflammation.

Keywords: Pacap (pituitary adenylate cyclase-activating polypeptide), Toxoplasma, Immune Modulation, Acute toxoplasmosis, Monocytes

Received: 31 Jan 2019; Accepted: 26 Apr 2019.

Edited by:

Nicolas Blanchard, INSERM U1043 Centre de Physiopathologie de Toulouse Purpan, France

Reviewed by:

Gaoqian Feng, Burnet Institute, Australia
Dumith C. Bou-Habib, Oswaldo Cruz Foundation (Fiocruz), Brazil  

Copyright: © 2019 Figueiredo, Düsedau, Steffen, Gupta, Dunay, Tóth, Reglodi, Heimesaat and Dunay. 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. Ildiko R. Dunay, Medizinische Fakultät, Universitätsklinikum Magdeburg, Magdeburg, Saxony-Anhalt, Germany,