Thursday, December 18, 2014

Trypanosoma cruzi

By Noora Hussain


The human body has an army at the ready to attack and protect itself from invaders. This army is called the immune system. It is equipped with weapons that span the physical body, are effective against many different types of attacks, and are organized in such a way that allows for strategic interactions which amplifies the body’s defenses. When a parasite wages war on the body, the body’s army goes into battle with full force. Winning results in successful elimination of the parasite from the body, but may leave the immune system weakened. Losing the battle can result in disease. Parasites have their own arsenal of weapons, which allows them to defeat the immune system. Parasites have mechanisms that shield them from host’s defenses and have ways to attack specific target cells. One such parasite that wields its own sword and shield is Trypanosoma cruzi. This motile protozoan pathogen is the causative agent of Chagas disease.1 Chagas disease affects the cardiac and digestive systems of the body and can cause acute or chronic infections2.  The parasite T. cruzi uses offensive mechanisms to counterattack a host cell’s defenses.
Chagas disease affects eight million people in Latin America.2 The disease was discovered in 1909 by the Brazilian physician Carlos Chagas, who named the parasite after his mentor Oswaldo Cruz.3 Chagas disease can cause acute or chronic infection that affects many different cells of the body.2 Clinical manifestations of acute infections include myocarditis, pericardial effusion, or meningoencephalitis.3 After the initial acute stage subsides, the diseases enters the chronic stage.3 Most patients can survive with the chronic infection, but a small percentage of patients develop cardiomyopathies within a year.3 Infection by T. cruzi occurs in a cycle and involves blood sucking insect vectors belonging to the Reduviidae family. 4 From the insect, the parasite comes into contact with a human or a wild animal.2 Then, it goes back to the insect when the insect feeds off the infected human.2 When the blood sucking insect lands on skin to feed, it also defecates in that spot leaving behind T. cruzi infected feces.5 Fecal droplets can get passed inside of humans through mucosa or through breaks in the epithelial barrier.5 T. cruzi can also infect through oral transmission with infected foods.5 Another much less common transmission mechanism is from blood transfusion.5 Congenital transmission from infected mother to child is also possible, but like blood transfusions is not a very common mechanism.5
Trypomastigotes are the infectious forms of T. cruzi and they infect the endothelial and mucosal cells of humans and other mammals.6 They invade these cells in order to differentiate and replicate inside of the host cell lysosome and cytoplasm.6 The invasion mechanism of T. cruzi is unique because it uses the host cell machinery that would generally be used against a protozoan parasite. T. cruzi trypomastigotes are highly motile7. A flagellum is attached to the cell body of T. cruzi, which enables the parasite to move on its own.8 Active motility of T. cruzi is a mechanism that the parasite uses to penetrate through the host cell membrane.9 After it gains entry, the host cell is infected.9 Once the host cell is infected, the trypomastigotes undergo cytokinesis, but their nuclei do not divide.9 The division occurs towards the back end of the basal body where the flagellum is attached.9 Through this process, the unnecessary flagellum is discharged into the host cell cytoplasm where it is then degraded.9 
The surface of T. cruzi provides a shield for the parasitic pathogen. This enables the parasite to travel throughout the body without being defenseless against the host’s immune system. The major surface components of T.cruzi provide the parasite with protection against the host’s cell defenses and enables the parasite to adhere to specific target cells for invasion.5 Mucin is a glycoprotein and one of the major surface components that plays a role in infection.1 Mucin sticks out from the outer phospholipid layer of T. cruzi’s plasma membrane.5 They are anchored  to the plasma membrane by glycosylphosphatidylinositol (GPI).1 These GPI-anchored glycoproteins cover the majority of the T. cruzi’s surface.5 Mucins recognize and target endothelial cells for invasion.5  They attach themselves onto the lipid bilayer of host cells.10 A signal is transduced that directs the glycoprotein into the cytoplasm and to the endoplasmic reticulum of the host cell.10 Once inside the host cell, T. cruzi can also interact with other organelles in the cytoplasm and use them to mediate infection.10
Host cells have lysosomes to remove unwanted material from inside of their cells. Normally, a lysosome would ingest, destroy, and secrete an invading pathogen. However, upon infection, T. cruzi’s plasma membrane fuses with the host cell lysosome, creating what is called a lysosome derived parasitophorous vacuole.6 The formation of the parasitophorous vacuole anchors the parasite to a structure of the host.6 The anchored parasite can undergo replication before disseminating into the host’s bloodstream and throughout the body.6 T. cruzi interacts with lysosomes of the  host cell because they have a low pH value.6  Having a highly acid organelle is a defense weapon of the host, but is used against the host when it facilitates trypomastigotes differentiation, replication, and dissemination.6 The parasitophorous vacuole membrane is disrupted and the acidic environment can have its full effect on the trypomastigotes.6  Disruption of the membrane is caused by the release of the pore forming molecule TcTox from trypomastigotes.6 Release of this molecule is triggered by the lysosome’s acid environment.6  Acidity also serves as a trigger to initiate differentiation of trypomastigotes into amastigotes.6 Amastigotes replicate, exit the lysosome, and disseminate into the blood stream.3 This spreads infection to other cells of the body.3-6
            The outcome of a battle between a parasite and the human body is critically important. A human’s immune system is well equipped to defend against many infections. However, parasites have developed mechanisms that provide them with a good offense and can retaliate against the immune system. So, in a battle between the two, the immune system does not always defeat the invader and the parasite can conquer and win.  

References
  1. Gonzalez MS, Souza MS, Garcia ES, Nogueira NFS, Mello CB, et al. (2013) Trypanosoma cruzi TcSMUG L-surface Mucins Promote Development and Infectivity in the Triatomine Vector Rhodnius prolixus. PLoS Negl Trop Dis 7(11): e2552. doi:10.1371/journal.pntd.0002552
  2. Rassi Jr, A., Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. The Lancet, 375(9735), 17-23. doi:10.1016/S0140-6736(10)60061-X
  3. Pereira Nunes, M. C., Dones, W., Morillo, C. A., Encina, J. J., & Ribeiro, A. L. (2013). Chagas Disease. Journal of the American College of Cardiology, 62(9), 767-776. Retrieved from https://www-clinicalkey-com.ezp2.lib.umn.edu/#!/content/playContent/1-s2.0-S073510971302250X
  4. Prata, A. (2001). Clinical and epidemiological aspects of Chagas disease. Lancet Infectious Diseases, 1(2), 91-100. doi:10.1016/S1473-3099(01)00065-2
  5. Campo, V. A., Frasch, A. C., Buscaglia, C. A., & Noia, J. M. (2006). Trypanosoma cruzi surface mucins: host-dependent coat diversity. Nature Reviews Microbiology, 4, 229-236. doi:10.1038/nrmicro1351
  6. Burleigh, B. A. and Woolsey, A. M. (2002), Cell signalling and Trypanosoma cruzi invasion. Cellular Microbiology, 4: 701–711. doi: 10.1046/j.1462-5822.2002.00226.x
  7. Andrade, L. O., & Andrews, N. W. (2005). The Trypanosoma cruzi–host-cell interplay: location, invasion, retention. Nature Reviews Microbiology, 3, 819-823. doi:10.1038/nrmicro1249
  8. Sacks, D. (2014). Lost but Not Forgotten. Cell Host & Microbe, 16(4), 423-425. doi:10.1016/j.chom.2014.09.017
  9. Kurup, S. P., & Tarleton, R. L. (2014). The Trypanosoma cruzi Flagellum Is Discarded via Asymmetric Cell Division following Invasion and Provides Early Targets for Protective CD8+ T Cells. Cell Host & Microbe, 16(4), 439-449. doi:10.1016/j.chom.2014.09.003
  10. Canepa, G. E., Mesias, A. C., Yu, H., Chen, X., & Buscaglia, C. A. (2012). Structural Features Affecting Trafficking, Processing, and Secretion of Trypanosoma cruzi Mucins. The Journal of Biochemistry, 287, 26365-26376. doi: 10.1074/jbc.M112.354696

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