Immunomodulatory effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide in acute toxoplasmosis

Caio Andreeta Figueiredo, Henning Peter Düsedau, Johannes Steffen, Nishith Gupta, Miklos Pal Dunay, G. Tóth, D. Reglodi, Markus M. Heimesaat, Ildiko Rita Dunay

Research output: Contribution to journalArticle

Abstract

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 regulating macrophages and monocytes inhibiting the production of inflammatory cytokines, chemokines and free radicals. Here, we analyzed the effect of exogenous PACAP on peripheral 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 interfere 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 treatment, interleukin (IL)-10 and Transforming growth factor beta (TGF-β) remained stable. While PACAP modulated VPAC1 and VPAC2 receptors in 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.

Original languageEnglish
Article number154
JournalFrontiers in Cellular and Infection Microbiology
Volume9
Issue numberMAY
DOIs
Publication statusPublished - Jan 1 2019

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Pituitary Adenylate Cyclase-Activating Polypeptide
Toxoplasmosis
Neuropeptides
Toxoplasma
Monocytes
Receptors, Vasoactive Intestinal Peptide, Type II
Parasites
Receptors, Vasoactive Intestinal Polypeptide, Type I
Cytokines
Host-Pathogen Interactions
Nerve Growth Factor Receptor
Parasitic Diseases
Brain-Derived Neurotrophic Factor
Peritoneal Cavity
Chemokines
Transforming Growth Factor beta
Interleukin-10
Free Radicals
Macrophages
Inflammation

Keywords

  • Acute infection
  • Innate immunity
  • Macrophages
  • Monocytes
  • Neurotrophins
  • Pituitary adenylate cyclase-activating polypeptide (PACAP)
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Immunomodulatory effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide in acute toxoplasmosis. / Figueiredo, Caio Andreeta; Düsedau, Henning Peter; Steffen, Johannes; Gupta, Nishith; Dunay, Miklos Pal; Tóth, G.; Reglodi, D.; Heimesaat, Markus M.; Dunay, Ildiko Rita.

In: Frontiers in Cellular and Infection Microbiology, Vol. 9, No. MAY, 154, 01.01.2019.

Research output: Contribution to journalArticle

Figueiredo, Caio Andreeta ; Düsedau, Henning Peter ; Steffen, Johannes ; Gupta, Nishith ; Dunay, Miklos Pal ; Tóth, G. ; Reglodi, D. ; Heimesaat, Markus M. ; Dunay, Ildiko Rita. / Immunomodulatory effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide in acute toxoplasmosis. In: Frontiers in Cellular and Infection Microbiology. 2019 ; Vol. 9, No. MAY.
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