Toxoplasma Parasite Opens New Doors For Disease Research

Biologists define parasitism as a relationship where one organism benefits in the course of taking advantage of another. By understanding how parasites prey on their hosts, medical researchers could develop some novel ways to fight disease. That's one idea Laura Knoll, an associate professor of medical microbiology and immunology at the University of Wisconsin-Madison, explores in her work with Toxoplasma gondii, the single-celled protozoan parasite best known for causing toxoplasmosis.

Knoll explained basic concepts of parasitism and symbiosis in a January 8, 2014 talk at the Wednesday Nite @ the Lab lecture series at UW-Madison, recorded for Wisconsin Public Television's University Place. Using T. gondii's relationship with cats and dependence of the malaria-causing protozoan genus Plasmodium on mosquitoes as examples, she shed light on the complex and varied life cycles of parasitic organisms. Knoll also discussed this biological information in the context of the billions of beneficial microorganisms that help humans and other multicellular organisms, including humans, carry out vital processes like digestion.

Focusing on on Toxoplasma, Knoll described how she and other researchers are trying to isolate specific proteins in the organism that can trigger specific immune responses in lab mice — and perhaps eventually in humans. By understanding how parasites can manipulate of the immune system, Knoll hopes to develop immunotherapies that can target antibiotic-resistant bacteria, or even temper the overactive immune responses that make many diseases even more dangerous.

Key facts

• Symbiotic relationships are classified in three ways: mutually beneficial (mutualism); benefiting one and neutral for the other (commensalism); and beneficial to one and harmful to another (parasitism). There are 10 times more microbial cells in a human body than there are human cells. These organisms are called a microbiota.


• The human body's relationship with its microbiota is usually stable, but antibiotics can throw it out of balance, as can problems with the immune system.


• One way parasites are classified is by the location of their relationship with hosts. Parasitic organisms living inside the body are termed endoparasites, like worms, and those on the skin are ectoparasites, like ticks.


• Two types of endoparasites colonize humans: Protozoans (single-celled organisms) and helminths (multi-cellular worms).


• For the most part, humans' relationships with parasites are accidental, where the host is not an integral part of a parasite's life cycle.


• Many people know they can be exposed to Toxoplasma by handling cat litter, but most human exposures are through eating or handling undercooked meat.


• Animals with a chronic toxoplasmosis infection have more protection against other pathogens, even the H5N1 influenza virus, which suggests a more mutualistic relationship. It's in the parasite's biological interest that the host stays healthy and continues moving around in its environment. The longer the host remains active, the more likely it is to get preyed upon and the parasite passed on.


• Researchers have found that extracts of Toxoplasma proteins can be used as a treatment for influenza viruses and cerebral malaria. Knoll hopes to learn if Toxoplasma infection can guard against cancer, but research in this area is only beginning.


• Researchers know that immune response and metabolism are connected in humans and animals with similar physiologies, but don't yet understand yet how this dynamic works.

Key quotes

• On correcting the colloquial definition of "symbiosis": "A biological definition of symbiosis is two distinct organisms or species in close association with each other. So we usually think of it as the mutualistic or beneficial relationship, but it's actually just that close relationship."


• On the relationship between human bodies and the microbes that live in them: "We're really an ecosystem. I try to think of myself as an ecosystem."


• On her choice of a research focus: "One of the reasons I got interested in parasitology is because of the complexity of their life cycles. It's absolutely fascinating developmental biology, and it just sort of amazed me how these things could evolve."


• On the potential advantages of immunotherapeutics: "If you're in the emergency room and you know you have some kind of infection, but you don't know what yet, or you're in some developing-world country and you don't have good diagnostic techniques there, you want something that you can be able to treat the patient with right away that would at least relieve their symptoms. So the advantage of immunotherapeutics like this is that they're broad-spectrum antimicrobial because they elicit an innate immune response, and they could be rapid in emergency situations before diagnosis was available, and you're less likely to get resistance because it's not an antibiotic that's targeting the microbe ... it could be used to treat antibiotic-resistant microbes."


• On the nature of cerebral malaria and many other similar diseases: "It's not really the microbe that's harming you. It's your body's over-reactive immune response to that microbe that's actually causing the disease. There's a real need for treatments that just quell that over-reactive immune response, but aren't so broad-spectrum that you have no immune response."