Kupffer cells survive Plasmodium berghei sporozoite exposure and respond with a rapid cytokine release

Rebecca E. Tweedell, Le Qi, Zhao Li Sun, Rhoel R. Dinglasan

Research output: Contribution to journalArticle

Abstract

The liver stage of the Plasmodium life cycle features sporozoite traversal of the liver sinusoidal barrier through Kupffer cells (KCs) followed by invasion of hepatocytes. Little is known about the interaction of Plasmodium sporozoites with KCs, the liver-resident macrophages. Previous reports suggest KCs do not mount a pro-inflammatory response and undergo cell death following this interaction. Our work explores this interaction using primary rat KCs (PRKCs) and Plasmodium berghei sporozoites. We analyzed PRKC culture supernatants for markers of an immunological response through cytokine arrays. Additionally, cell wounding and death were assessed by monitoring lactate dehydrogenase (LDH) levels in these supernatants and by live/dead cell imaging. We found that PRKCs mount an immunological response to P. berghei sporozoites by releasing a diverse set of both pro-and anti-inflammatory cytokines, including IFNγ, IL-12p70, Mip-3α, IL-2, RANTES, IL-1α, IL-4, IL-5, IL-13, EPO, VEGF, IL-7, and IL-17α. We also observed no difference in LDH level or live/dead staining upon sporozoite exposure, suggesting that the KCs are not deeply wounded or dying. Overall, our data suggest that sporozoites may be actively modulating the KC’s reaction to their presence and altering the way the innate immune system is triggered by KCs.

Original languageEnglish (US)
Article number91
JournalPathogens
Volume7
Issue number4
DOIs
StatePublished - Dec 1 2018

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Plasmodium berghei
Sporozoites
Kupffer Cells
Cytokines
Plasmodium
L-Lactate Dehydrogenase
Liver
Cell Death
Interleukin-7
Chemokine CCL5
Interleukin-13
Interleukin-17
Interleukin-5
Life Cycle Stages
Interleukin-1
Interleukin-4
Vascular Endothelial Growth Factor A
Interleukin-2
Hepatocytes
Immune System

Keywords

  • Cell death
  • Cytokines
  • Innate immunity
  • Kupffer cell
  • Malaria
  • Plasmodium berghei
  • Sporozoite

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Kupffer cells survive Plasmodium berghei sporozoite exposure and respond with a rapid cytokine release. / Tweedell, Rebecca E.; Qi, Le; Sun, Zhao Li; Dinglasan, Rhoel R.

In: Pathogens, Vol. 7, No. 4, 91, 01.12.2018.

Research output: Contribution to journalArticle

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