Evasion strategies of Plasmodium falciparum (Malaria) by Xiaomeng Yang https://padlet.com/xiaomy/8vlhppctf8vheo7a Introduction to malaria, infection cycle of malaria, two stages of malaria: exoerythrocytic and erythrocytic stages, evasion strategies of Plasmodium falciparum en-us 2020-12-07 00:18:33 UTC 2025-04-24 13:29:20 UTC hello@padlet.com Introduction to Malaria yuyingliuw1013 https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992395942 Malaria is transmitted by the female Anopheles mosquito during a feeding. As the mosquito feeds on its host, sporozoites are released into the bloodstream, and they migrate to the liver. When the parasites mature, they leave the liver and infect red blood cells. The hepatocyte EphA2 receptor was critical for establishing a permissive sporozoite intracellular replication compartment in the liver. The complete life cycle of Plasmodium requires two hosts: the mosquito vector and the vertebrate host.]]> 2020-12-07 00:26:57 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992395942 Infection cycle of Malaria xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992402297 2020-12-07 00:31:12 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992402297 Strategies to evade first barrier -- skin as an immune system xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992429624 The skin is the first barrier that parasites encountered after transmission into the vertebrate host. Sporozoites of Plasmodium falciparum have evolved to overcome this barrier by mechanical strategies such as motility and cell transversal. Specialized proteins such as SPECT-1 and SPECT-2 (sporozoite microneme protein essential for cell traversal) prevent the sporozoites from being blocked by demis or being ingested by phagocytes.
The sporozoites can also traverse immune cells, leading to the inactivation of immune cell defenses and preventing the clearance of sporozoites by exocytosis before crossing the barrier. 
Another protein responsible for motility of sporozoites is TRAP (Thrombospondin-Related Anonymous Protein). This protein is found on the micronemes and the surface of sporozoites. TRAP allows the parasite to interact with surface host molecules that provide gliding motility to exit the dermis. ]]> 2020-12-07 00:47:22 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992429624 Erythrocytic evasion strategies --Antigenic diversity and Sequestration yuyingliuw1013 https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992436593 PfEMP-1, RIFIN, and STEVOR multigene families mediated intraerythrocytic evasion. These proteins create rosettes that help them to bind on red blood cell epitopes and avoid immune recognition. Expression of PfEMP1 could enhance the infected red blood cell's ability to bind different host cells. The antibody IgM is not specific for the parasites. The binding of IgM to PfEMP 1 helps the parasites preventing splenic elimination. The binding also helps to sequester sporozoites in the microvasculature of various organs.
CD4+ T cells produce proinflammatory cytokines that activate macrophages. NK cells also activated and secreting IFN-γ, perforin, and granzyme to kill P. falciparum-infected RBCs.]]> 2020-12-07 00:51:27 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992436593 Exoerythrocytic evasion strategies & ways for immune system to fight back-- from skin to liver xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992526587 After the sporozoites migrate from the skin, crossing all cellular barriers, they will reach the blood, and consequently the lymphatic system. Once inside the circulatory system, sporozoites rapidly reach the sinusoid cavity of the liver. The exoerythrocytic (liver) stage has been described as asymptomatic because the liver is an immune privileged organ that is protected against a strong immune response.
Even though the liver stage was considered an unresponsive phase, there are the liver immune cells presented and activated during the liver stage. Plasmodium RNA could activate the type I interferon (IFN) pathway via the cytosolic Pattern Recognition Receptor (PRR), MDA5. Type I interferons are potent inflammatory cytokines that are known to inhibit growth of exoerythrocytic forms. Natural Killer and Natural Killer T cells (NK, NKT), and γδT cells also involve in the mediation of anti-parasitic effects through secretion of type I interferons and IFN-γ. Other molecules such as hepcidin have been implicated in growth inhibition of exoerytrhrocytic phases. ]]> 2020-12-07 01:40:53 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992526587 Exoerythrocytic evasion strategies -- Kupffer cells xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992550510 To invade hepatocytes, sporozoites must cross the barrier lined by endothelial cells (ECs) and immune phagocytic cells called Kupffer Cells (KCs). Sporozoites can pass through gaps between ECs and KCs, not engaging in traversal capacity.
The sporozoites can also go through KCs and modulate their cytokine profile, leading to the downregulation of Th1 cytokines (TNF-α, IL-6, and MCP-1) and the upregulation of Th2 cytokines (IL-10) for ensuring safe passage.
Additionally, the binding of sporozoites to KCs also promotes apoptosis of KCs and decreases the expression of MHC I and IL-12. This results in T cell tolerance. Lack of MHC-I would help the parasite to void recognition by CD8+ T cells.
Finally, the circumsporozoite protein (CSP) on the sporozoites can interact with LRP-1 (low-density lipoprotein receptor-related protein) and proteoglycans on the KC surface, increasing the levels of intracellular cAMP/EPAC, and preventing the formation of reactive oxygen species (ROS) which can cause cellular damage and kill the parasite. ]]> 2020-12-07 01:54:15 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992550510 Exoerythrocytic evasion strategies -- hepatocytes xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992594986 The sporozoites release CSP to modulate the host inflammatory response through the suppression of the NF-κB signaling pathway and the upregulation of host heme oxygenase-1 (HO-1). This further promotes the parasite development in the liver. Sporozoite infection of hepatocytes also interferes with the mTOR pathway, which alters the levels of proteins involved in cell survival, proliferation, autophagy, anabolism, and cell growth.
After invading the final hepatocyte, sporozoites are enclosed in a parasitophorous vacuole (PVM), which physically separates it from the host cytoplasm thereby avoiding degradation by the endocytic/lysosome system. This isolation keeps the parasitophorous vacuole isolated from cell intrinsic defenses such as apoptosis and selective autophagy. ]]> 2020-12-07 02:20:46 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992594986 Exoerythrocytic vs. Erythrocytic xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992613943 Exoerythrocytic stage: A stage in the life cycle of the malaria parasite found in liver cells (hepatocytes). Exoerythrocytic stage parasites do not cause symptoms.
Erythrocytic stage: A stage in the life cycle of the malaria parasite found in the red blood cells. Erythrocytic stage parasites cause the symptoms of malaria.]]> 2020-12-07 02:31:17 UTC https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992613943 Sources xiaomy https://padlet.com/xiaomy/8vlhppctf8vheo7a/wish/992636984 Esmael Besufikad Belachew, "Immune Response and Evasion Mechanisms of Plasmodium falciparum Parasites", Journal of Immunology Research, vol. 2018, Article ID 6529681, 6 pages, 2018. https://doi.org/10.1155/2018/6529681
Gomes, Pollyanna S et al. “Immune Escape Strategies of Malaria Parasites.” Frontiers in microbiology vol. 7 1617. 17 Oct. 2016, https://doi.org/10.3389/fmicb.2016.01617
Kaushansky, Alexis, et al. “Malaria Parasites Target the Hepatocyte Receptor EphA2 for Successful Host Infection.” Science, American Association for the Advancement of Science, 27 Nov. 2015, https://doi.org/10.1126/science.aad3318
https://www.cdc.gov/malaria/glossary.html
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