In the microbiology article, "Interactions of the malaria parasite and its mammalian host" by Silvie, et al., it explains about the protist causing disease Malaria. To be more specific it talks about the parasitic interactions it may have with its mammalian host. Malaria is a huge problem in underdeveloped countries, like Africa, and because it is mainly transmitted by Anopheles mosquitoes, it is also mostly uncontrollable. In the article, due to rodent in vivo models, and live imaging, many were able to shed some detail on the parasitic malaria and mammalian host contact.
As explained before, malaria can be transmitted by the Anopheles mosquito. Particularly by the insect's stinger or vector injecting the Plasmodium sporozoites, via its saliva, into a mammal's skin. At this stage the sporozoite's prime destination is to get to the liver. However many are degraded by lymph nodes, eaten by phagocytes, or if they are lucky encounter a blood vessel to enter, so they can catch a ride to the liver. In order to find a blood vessel sporozoite cells have to travel in a random fashion, and three parasitic proteins are found to aid in that routine so far; SPECT-1, SPECT-2, and a phospholipase. Once inside they can start the invasion process which involves sporozoites covered with circumsporozoite protein (CSP) migrating through hepatocytes by interacting with heparin sulfate proteogylcans (HSPGs) on liver cells. Then a parasitophorous vacuole (PV) can be formed.
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Studies have been shown that the sporozoite's progression from migrating to actively invading may slow down the intended infection. SPECT mutants do not transmigrate, and as a result these abnormal sporozoite cells invade more rapidly than the normal ones. Also HSPGs with high sulfate content may be a factor as well, as it makes the cells more prone to switch to infection in the liver. Moreover, hepatocyte receptors may also be helping along sporozoite entry, along with other unknown sporozoite molecules.
Continuing the invasion, the sporozoites multiply into merozoites stationed inside the PV membrane (PVM). Then they are unrestricted into the bloodstream by the liver's hepatocytes. Rodents infected with Plasmodium yoelii were observed by a live microscopy analysis to have the merosomes exit the liver as a whole product before releasing the merozoites. This process was simplified by a no hassle siege of the host's cell. The host's cell is beneficial to Plasmodium because it allows for undetection and an easy supply of nutrients. To be even more effect, this parasite has various proteins for the optimal survival. Some examples include CSP, which provides favorable conditions for Plasmodium, and newer identified proteins like UIS3, UIS4, and Pb36p. In recent studies UIS3 interacted with L-FABP, a liver-fatty acid binding protein in vitro. Fatty acids may be needed in its liver stages, and when there is a limited resource of it then parasitic development is restricted.
The Plasmodium parasites invade the red blood cells (RBCs) next. This process happens in seconds with the help of receptor-ligand interactions. Initial attachment to the RBCs is helped along by the merozoite surface proteins (MSPs) like MSP1, and the apical membrane antigen-1 (AMA-1). For penetration erythrocyte binding antigens (EBAs) and Plasmodium falciparum reticulocyte-binding homologs (PfRHs) are used, while at the same time forming a PV. Merozoite entry into the erythrocyte is diverse and plentiful, and due to a study in Kenya these other pathways are used by many normal parasites.
However once they enter the RBCs they have to provide a way to receive the food and nutrients needed by expanding their surface area with a tubovesicular network and by mediating proteins like FIKK/TSTK through the Plasmodium export element (PEXEL) or host targeting (HT). This allows for the parasite to be sustained while expanding.
In a study with mice infected with Plasmodium berghei ANKA, levels of heme oxygenase-1 (HO-1) and carbon dioxide were observed to determine whether or not they exhibited CM, or cerebral malaria. Lower levels of HO-1, promoted CM to be expressed whiles the introduction of inhaled CO protected mice against it. Also factors that stop HO production or deletes Hmox1 activity increased the occurrence of CM, and factors that induced HO, like NO decreased the chance of CM. HO-1 was also seen in the liver and pathology stage of infection from the observation of mice. In the liver there was a high concentration of HO-1, and if reversed with a down regulation of HO-1 and a deletion of Homx1, there would be no infection. Therefore HO-1, a host molecule controls the infection of the liver and red blood cells.
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Overall according to the article, understanding host interactions with the Plasmodium parasite gives insight in to how these stages or processes might be stopped or restricted using a vaccine. Genetically attenuated parasites (GAPs), or coevolution of a parasite's receptor-ligand interactions to its host could be used as a strategy in determining a vaccine. Knowing the levels of HO-1 and CO can determine whether CM will be expressed in infected individuals with Plasmodium berghei ANKA, and it can control the Plasmodium effectiveness in the liver or pathology stage.
In my opinion these kinds of studies are significant in determining whether an aspect like how a parasite interacts with its host could be used as a strategy for vaccine formation. Having great minds think on a microbial level, as well as environmental improves our chances of succeeding. For further research I would look more into the egress stage, and see if there are ways to keep it from infecting nearby cells. In other words I would like to find a way to keep the parasite contained until the pathogen is killed in infected hosts.
Although malaria is not really a problem in North America, finding solutions to any type of problem will be beneficial to all mankind. Checking one thing off a list of hundreds or even thousands problems makes us one step closer to an ideal world.