During malaria, why don't Kupffer cells (hepatic macrophages) attack the Plasmodium sporozoites and stop schizogony, thus saving us from the disease?

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    $\begingroup$ I assume the parasite has developed some coating to prevent Kupffer cell uptake, but I don't know what. Of course, once it enters a blood cell, Kupffer cells uptake won't be an issue anymore. This might be interesting to look at in more detail, people doing nanoparticle research are also interested in making particles avoid Kupffer cell uptake while getting hepatocyte uptake. $\endgroup$ – user137 Mar 9 '16 at 3:51
  • $\begingroup$ I know only tardigrade is only being capable of creating bio-glass coating to prevent itself being dessicated.I didn't know sporozoite having same capability. $\endgroup$ – Swastik Mar 10 '16 at 12:14

Indeed the process is even more interesting than thought: sporozoites actively attack Kupffer cells and let themselves get eaten! In a 2001 research, Pradel et al found that sporozoites pass through a layer of Kupffer cells in order to enter hepatocytes for the next stage of their life cycle. They observed that in rat liver cells, Plasmodium berghei and Plasmodium yoelii sporozoites attach to and enter the Kupffer cells, but not the sinusoidal endothelia. During experiment, the number of intracellular sporozoites kept increasing for upto 12 hours, unlike hepatocytes and other non-phagocytic cells which were invaded in vitro for only the first hour of parasite exposure. The sporozoites entered the Kupffer cells via endocytosis in specialized vesicles which did not interact with lysosomal markers. From Kupffer cells, sporozoites traversed to hepatocytes where they developed into exoerythrocytic schizonts. In another 2015 research, Cha et al concluded that the sporozoites interact with CD68 receptor on the surface of Kupffer cells for endocytosis. In short, sporozoites literally pass through Kupffer cells without letting Kupffer cells doing any harm to them. See this diagram for illustration:


EDIT: What happens in Kupffer cells during traversal of sporozoites remains unkown to some extent. However, Frevert et al, 2008 has shown that sporozoites render Kupffer cells insensitive to pro-inflammatory stimuli and force them towards apoptosis (aka programmed cell death or "cell suicide"). This happens as sporozoite-exposed Kupffer cells are stimulated by lipopolysaccharide or IFN-$\gamma$, causing down-modulation of TNF-$\alpha$, IL-6 and MCP-1 and upregulation of IL-10. Nuclear factor NF-$\kappa$B is also activated, which causes apoptosis in Kupffer cells (Punsawad et al, 2014). However, if Kupffer cells are activated, in particular by immunization caused due to high antivody levels, they may phagocytoze the sporozoites and thus prevent their traversal (Krzych et al, 2015).


  1. Pradel, G. and Frevert, U. (2001), Malaria sporozoites actively enter and pass through rat Kupffer cells prior to hepatocyte invasion. Hepatology, 33: 1154–1165. doi:10.1053/jhep.2001.24237

  2. Cha, S.-J., et al. CD68 acts as a major gateway for malaria sporozoite liver infection. J. Exp. Med., July 2015 DOI: 10.1084/jem.20110575

  3. Klotz C, Frevert U. Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells. International journal for parasitology. 2008;38(14):1639-1650. doi:10.1016/j.ijpara.2008.05.018

  4. Viriyavejakul P, Khachonsaksumet V, Punsawad C. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression. Malaria Journal. 2014;13:106. doi:10.1186/1475-2875-13-106.

  5. Frevert U, Krzych U. Plasmodium cellular effector mechanisms and the hepatic microenvironment. Frontiers in Microbiology. 2015;6:482. doi:10.3389/fmicb.2015.00482.

  • $\begingroup$ Does the Kuppfer Cells get affected while letting sporozoites pass through them? @another 'Homo Sapien' $\endgroup$ – Swastik May 8 '17 at 4:12
  • $\begingroup$ Does the Kupffer cells get affected while letting the sporozoites pass through them? $\endgroup$ – Swastik May 8 '17 at 4:14
  • $\begingroup$ @swastik I've that part in the answer. If you have any further queries, please ask them here or add them in your question with an "EDIT" :) $\endgroup$ – another 'Homo sapien' May 8 '17 at 9:00

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