Symptoms such as fever and chills are indictors of the Plasmodium parasite invading the red blood cells (RBCs) which indicates that the parasite has started the rapid asexual replication. Malaria can cause anemia, acute respiratory distress and cerebral malaria. Malaria is one of the most infectious diseases because of its way of transmission. The transmission of malaria occur trough vectors by the Anopheles mosquito injecting the sporozoites. The significance of this study is to be able to understand the parasite-host interactions in regards to genetic basis. This study can be useful in identifying the target cell recognitions, its nutrient acquisition, and high jacking the immune functions using in vivo rodent models.
Malaria has different invasion stages of infection, it begins with the skin and leaks its way through the blood vessels, liver and then to its final destination the RBCs. The invasion first starts with the Anopheles mosquito injecting the plasmodium sporozoites into the skin. The sporozoites can have three courses of action; the first course of action is to randomly move until it reaches blood vessels, secondly the ones that remain in the skin unable to go anywhere will eventually be eliminated by phagocytes, and last course of actions are those Plasmodium's that will enter the lymphatic circulation where they will also get degraded. During these stages of invasion the immune response began to build a protective response against the Plasmodium sporozoite. During the skin invasion as the sporozoites are migrating, it is known that the sporozoites require at least three different parasite proteins during the sporozoite transversal called sporozoite protein essential for cell transversal (SPECT)-1, SPECT-2 and phospholipase. The sporozoites that remain in the skin unable to go anywhere are trapped because they lack one of these proteins that are necessary for migration. The sporozoites that are lucky enough to enter the blood stream will quickly settle in the liver with the help of the circumsporozoite protein (CSP), this protein protects the surface of the sporozoite and can begin to invade the host without rupturing the host cell plasma membrane and will result in formation of parasitophorous vacuole (PV)
Once the sporozoite has reached the liver it will then began to multiply and turn into merozoites which remain in the parasitophorous vacuole membrane (PVM) until they are released from the liver into the bloodstream. The nutrients needed for the parasite to survive are more likely being gathered from the hepatocytes. The hepatocytes are also downregulating the inflammatory response so the immune system won't be able to identify it as a threat. In the past years it has been proved that Plasmodium requires UIS3, UIS 4 and Pb36p to have a normal development process and the parasites lacking these proteins would not be able to re-infect any host. This study also shows that the interaction between L-FABP and UIS3 could have an effect of the parasites development, if the L-FABP is downregulated than the development will decrease. The point of interaction occurs when the UIS3 is localized to the PVM, the L-FABP will interact with UIS3 and deliver fatty acids to the liver stages, and this study indicated that the delivery of fatty lipids is a very important stage for the development of the liver stage. Towards the end of the liver stage the Plasmodium parasites will evolve into merozoites which are found in the merosomes. Once the merozoites egress from the hepatocytes, the serine repeat antigens (SERA's) increase and it can be an indication that the merozoites will be invading the lungs and then find its way to the blood stream and initiate the asymptomatic infections. Once in the bloodstream the parasite will use stage specific parasite factors to create more invasive stages.
Plasmodium parasites will rapidly invade the red blood cells in which will require several steps involving multiple receptor ligand interactions. The initial attachment is mediated by the merozoites surface proteins (MSP's) especially with band 3 on the surface of the RBCs then the AMA-1 initiates the next event. The penetration is induced by two largely redundant parasite transmembrane proteins. PfRH's and EBa's allow an efficient entry to occur which can be used in maintaining a variety of invasion pathways. The lack of intracellular organelles in RBCs is to great advantage to pathogens because the RBCs will lack the ability to display antigens on their surfaces, but also being in the RBC can be a disadvantage because the lack of endocytic and secretory pathways won't allow the parasite to grow fast enough causing it to recruit host organelles for nutrient acquisition. The protein is mediated into the RBCs through the Plasmodium export element (PEXEL) or host targeting (HT) signal. As these studies continue this will allow for an explanation on how the evolvement of host restriction and coevolution of parasitic effector and host cell target proteins. The more RBCs can be studied and understood in a biological perspective, the easier it will be able to understand the development of Plasmodium. Understanding the composition of the PVM will be useful to understand how the interaction between the host and parasite. A study that was recently performed proved that the early transcribed membrane proteins (ETRAMP's) located on the PVM is the primary protein to form oligomers and indicate that there is an interaction between the host and the parasite.
Malaria has killed 1-3million people mainly in non-immune children. The use of rodent models is used to conduct and be able to identify the mechanisms used by this parasite. The study has shown that the mice infected with Plasmodium berghei ANKA are useful to understand the development of cerebral malaria (CM). This study has been able to prove that the CD36 is a major receptor in identifying the RBCs. It has also been showed that in infected mice it is also required to have histamine-mediated signaling, chemokine receptors in the brain, dendritic cells, and T cells subsets. Then, another study has shown that the rate at which the limiting enzyme in the catabolism of free heme can dictates the susceptibility to CM in mice. The heme oxygenase-1(HO-1) is upregulated, and the deletion of Hmox1 or the inhibition of HO is increased in CM. NO and CO protects the mice from CM because they prevent the disruption of the BBB, and prevent neuroinflammation. NO and Co will bind the heme and prevents its oxidation and the generation of free heme. HO-1 has been proved to control the establishment of Plasmodium in the liver and the development in the bloodstream of malaria.
The importance of this experiment is to gather enough information to be able to fight or avoid the spread of malaria. Malaria has caused 1-3 millions of deaths in the world, and being able to identify the symptoms properly and at the proper stage one can be able to prevent the progression of malaria. This parasite has killed and affected mainly non-immune children that are unable to fight this parasite. I believe that this study should continue to find the key proteins that help the parasite survive, and acquire a vaccine targeting those proteins and eliminating them would prevent further growth of the disease. Some of the information in this article was very unclear to me and I was unable to understand this information, I believe that a graph indicating the presence of the proteins at the different stages of the Plasmodium parasite would be easier to understand but besides that, this article was very informative on how hard it can be to come up with a vaccine or any knowledge on how other organisms survive.
