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.
Highlights
Malaria is a devastating disease that causes over 400,000 deaths per year, mainly among young children in sub-Saharan Africa [1]
Our data demonstrate that primary rat KCs (PRKCs) can mount a rapid and diverse cytokine response to sporozoite exposure
This PRKC response is remarkable since exposure to the well-characterized Kupffer cells (KCs) activator
Summary
Malaria is a devastating disease that causes over 400,000 deaths per year, mainly among young children in sub-Saharan Africa [1]. Following transmission from an infected female anopheline mosquito to the skin of a human during blood feeding, the Plasmodium parasite makes its way by gliding motility to blood vessels and enters the bloodstream to hone to the first site of invasion and development, the liver [2]. When studying the LS, it is important to consider sporozoite invasion of hepatocytes and the steps leading up to this event. Sporozoites must traverse the sinusoidal barrier, which contains liver endothelial cells. Post-harvest of banana: Opportunities and KCs2011, of infected mice is essential in promoting apoptosis of Plasmodium-infected hepatocytes [16], nges. Y.M.; Joyce, D.C.; Macnish, A.J. LS, Extension of the shelf life of banana fruit by 1-methylcyclopropene during the contributing to host resistance to reinfection [17], and that leukocytes in the liver can mbination with polyethylene.
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