Host cell death induced by the egress of intracellular Plasmodium parasites

Heussler, Volker; Rennenberg, Annika; Stanway, Rebecca R.

doi:10.1007/s10495-009-0435-6

Cited by 17 publications

(9 citation statements)

References 43 publications

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“…This release occurs following the rupture of the parasitophorous vacuole membrane, and leads to hepatocytes cell death [40]. This hepatocytes cell death contributes to the formation of merosomes and their budding through the endothelium into the blood vessel.…”

Section: When Should Cell Death Be Called Apoptosis?mentioning

confidence: 99%

Apoptosis induced by parasitic diseases

2010

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Fatalities caused by parasitic infections often occur as a result of tissue injury that results from a form of host-cell death known as apoptosis. However, instead of being pathogenic, parasite-induced apoptosis may facilitate host survival. Consequently, it is of utmost importance to decipher and understand the process and the role of apoptosis induced or controlled by parasites in humans. Despite this, few studies provide definitive knowledge of parasite-induced host-cell apoptosis. Here, the focus is on a consideration of host-cell apoptosis as either a pathogenic feature or as a factor enabling parasite survival and development.Cell death by apoptotic-like mechanisms could be described as a ride to death with a return ticket, as initiation of the pathway may be reversed, with the potential that it could be manipulated for therapeutic purposes. The management of host-cell apoptosis could thus be an adjunctive factor for parasitic disease treatment. Evidence that the apoptotic process could be reversed by anti-apoptotic drugs has recently been obtained, leading to the possibility of host-cell rescue after injury. An important issue will be to predict the beneficial or deleterious effects of controlling human cell death by apoptotic-like mechanisms during parasitic diseases.

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Section: When Should Cell Death Be Called Apoptosis?mentioning

confidence: 99%

Apoptosis induced by parasitic diseases

2010

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“…The study of malaria liver stage infection has focused primarily on Plasmodium-hepatocyte interactions during invasion, intracellular parasite growth, and parasite egress (2,23,24). Plasmodium sporozoites have been found to directly contact liver macrophages in the liver (9), modulating their cytokine profile (12).…”

Section: Discussionmentioning

confidence: 99%

TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection

Gonçalves

Rodrigues-Duarte

Rodo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2 −/− Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2 −/− mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupfferhepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite. M alaria liver stage infection is asymptomatic but is absolutely required in the progression of Plasmodium infection in the vertebrate host, preceding propagation of parasites in the blood and clinical manifestations of malaria (1, 2). Current efforts in therapy and vaccine development include strategies aimed at deterring infection at the liver stage, preventing subsequent clinical complications and malaria transmission (3, 4). During liver stage infection, one Plasmodium sporozoite develops into thousands of merozoites inside each infected hepatocyte (5). Identification of host genetic factors that control liver parasite expansion may help elucidate response mechanisms operating during liver stage infection.Gene deficiency models and gene expression studies focusing on hepatocyte infection have highlighted genes that control hepatocyte invasion and intrahepatocyte parasite expansion [e.g., CD81 (6), SR-B1 (7, 8)], but the mechanisms of host response to liver stage infection remain elusive. It has been proposed that sporozoites' ability to traverse liver macrophages (9) and/or hepatocytes (10) in the course of liver stage infection may favor the release of proinflammatory factors at liver sites of sporozoite expansion (11,12). Innate immune mechanisms might be involved in sensing Plasmodium sporozoites and in controlling liver stage infection (13).Mouse models of liver stage infection suggest that sporozoites induce a innate in...

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“…Plasmodium cysteine proteases are involved in a variety of biological processes, such as hemoglobin degradation, protein trafficking, rupture of membranes, host cell invasion, and egress from host erythrocytes and host hepatocytes [4]–[13]. Cysteine proteases are also believed to mediate the unusual form of programmed host cell death that occurs at the end of liver stage development and which clearly differs from classical apoptosis [13], [14]. Furthermore, cysteine proteases are essential for parasite development in the mosquito vector [15].…”

Section: Introductionmentioning

confidence: 99%

A Cysteine Protease Inhibitor of Plasmodium berghei Is Essential for Exo-erythrocytic Development

et al. 2014

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Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role of ICP in different life cycle stages, we generated a stage-specific knockout of the Plasmodium berghei ICP (PbICP). Excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual PbICP protein being detectable in sporozoites. The vast majority of these parasites invading a cultured hepatocyte cell line did not develop to mature liver stages, but the few that successfully developed hepatic merozoites were able to initiate a blood stage infection in mice. These blood stage parasites, now completely lacking PbICP, exhibited an attenuated phenotype but were able to infect mosquitoes and develop to the oocyst stage. However, PbICP-negative sporozoites liberated from oocysts exhibited defective motility and invaded mosquito salivary glands in low numbers. They were also unable to invade hepatocytes, confirming that control of cysteine protease activity is of critical importance for sporozoites. Importantly, transfection of PbICP-knockout parasites with a pbicp-gfp construct fully reversed these defects. Taken together, in P. berghei this inhibitor of the ICP family is essential for sporozoite motility but also appears to play a role during parasite development in hepatocytes and erythrocytes.

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Host cell death induced by the egress of intracellular Plasmodium parasites

Cited by 17 publications

References 43 publications

Apoptosis induced by parasitic diseases

Apoptosis induced by parasitic diseases

TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection

A Cysteine Protease Inhibitor of Plasmodium berghei Is Essential for Exo-erythrocytic Development

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