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Pathogens 2018, 7(4), 91; https://doi.org/10.3390/pathogens7040091

Kupffer Cells Survive Plasmodium berghei Sporozoite Exposure and Respond with a Rapid Cytokine Release

1
Cellular and Molecular Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
2
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
3
Emerging Pathogens Institute, Department of Infectious Diseases & Immunology, University of Florida, Gainesville, FL 32611, USA
4
Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
*
Author to whom correspondence should be addressed.
Received: 24 October 2018 / Revised: 20 November 2018 / Accepted: 21 November 2018 / Published: 24 November 2018
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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. View Full-Text
Keywords: Kupffer cell; Plasmodium berghei; sporozoite; innate immunity; cell death; malaria; cytokines Kupffer cell; Plasmodium berghei; sporozoite; innate immunity; cell death; malaria; cytokines
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Tweedell, R.E.; Qi, L.; Sun, Z.; Dinglasan, R.R. Kupffer Cells Survive Plasmodium berghei Sporozoite Exposure and Respond with a Rapid Cytokine Release. Pathogens 2018, 7, 91.

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