Monthly Archives: September 2011

How ‘promiscuous parasites’ hijack host immune cells

Sept. 19, 2011

By Carly Hodes

Toxoplasma gondii parasites can invade your bloodstream, break into your brain and prompt behavioral changes from recklessness to neuroticism. These highly contagious protozoa infect more than half the world’s population, and most people’s immune systems never purge the intruders.

Toxoplasma gondii

Toxoplasma gondii parasites, green, multiply inside an immune cell that lives in the brain.

Cornell researchers recently discovered how T. gondii evades our defenses by hacking immune cells, making it the first known parasite to control its host’s immune system. Immunologists from the College of Veterinary Medicine published the study Sept. 8 in PLoS-Pathogens, describing a forced partnership between parasite and host that challenges common conceptions of how pathogens interact with the body.

Eric Denkers

Dr. Eric Denkers

“Toxoplasma is an especially promiscuous parasite,” said Eric Denkers, professor of immunology. “It infects nearly all warm-blooded species, most nucleated cell types and much of the human population. Although it lives in vital brain and muscle tissues, it usually causes no obvious reaction. Infection can seriously harm people with weak immune systems, yet most hosts experience no overt symptoms because Toxoplasma has found a way to coerce cooperation.”

Famous for its manipulative powers, T. gondii has been shown to alter the brain chemistry of rodents so that they fearlessly pursue cats. Cats eat the rodents, delivering the parasites to their breeding ground in feline intestines. Similar manipulations have surfaced in human studies linking T. gondii infections to behavioral and personality shifts, schizophrenia and population variations, including cultural differences and skewed sex ratios. Denkers’ study maps T. gondii’s newfound ability to manipulate cells in the immune system at the molecular level.

Toxoplasma parasites

Toxoplasma parasites forming a walled cyst in a mouse brain, where they release chemicals that can affect behavior.

“We found that Toxoplasma quiets its host’s alarm system by blocking immune cells from producing certain cytokines, proteins that stimulate inflammation,” said Denkers. “Cytokines are double-edged swords: They summon the immune system’s reinforcements, but if too many accumulate they can damage the body they’re trying to defend. An unregulated immune response can kill you.”

When immune cells meet intruders, they release cytokines that summon more immune cells, which produce more cytokines, rapidly causing inflammation. T. gondii must allow cytokines to trigger enough of an immune response to keep its own numbers in check and ensure host survival. But too many cytokines cause an overwhelming immune response that could damage the host or eliminate the parasites.

cytokine production in uninfected immune cells

Green stain highlights cytokine production in uninfected immune cells. Cells infected with Toxoplasma parasites, orange, cannot make cytokines.

“Toxoplasma hijacks immune cells to enforce a mutually beneficial balance,” Denkers said. “Until recently we thought it walled itself away inside cells without interacting with its environment. It’s now clear that the parasite actively releases messages into cells that change cell behavior.”

To prove this, Barbara Butcher, a senior research associate working with Denkers, exposed immune cells in the lab to bacterial factors that typically stimulate the release of inflammatory cytokines.

“Cells infected with Toxoplasma produced no messages to trigger inflammation,” Denkers said. “Our colleagues at Stanford University found that Toxoplasma produces a specific protein called ROP16 to suppress inflammatory responses. Collaborating with parasitologists at Dartmouth Medical School, we found that Toxoplasma sends ROP16 to infiltrate communication channels in immune cells, causing them to lower cytokine production.

“We are excited to have found the first non-bacterial pathogen able to exert this kind of control,” said Denkers. “If Toxoplasma can do this, maybe other parasites can too. This is the first case where the whole process of immune system manipulation is close to being completely mapped out at the molecular level.”

That map may help steer future investigations into how pathogens interact with hosts, unveiling the inner workings of a spectrum of infectious diseases.

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

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Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/toxoplasma.cfm

Media Hits:

Cornell Chronicle

http://www.vet.cornell.edu/news/toxoplasma.cfm

Answerclopedia

http://answerclopedia.com/promiscuous-parasites-hijack-host-immune-cells.html

Medical Xpress

http://medicalxpress.com/news/2011-09-promiscuous-parasites-hijack-host-immune.html

MyScience

http://www.myscience.cc/news/promiscuous_parasites_hijack_host_immune_cells-2011-cornell

Times of India

http://timesofindia.indiatimes.com/life-style/health-fitness/health/Promiscuous-parasites-make-you-reckless/articleshow/10079594.cms

NewKerala

http://www.newkerala.com/news/2011/worldnews-72626.html

LabSpaces

http://www.labspaces.net/113581/Researchers_discover_how__promiscuous_parasites__hijack_host_immune_cells

TopNews.in

http://www.topnews.in/health/promiscuous-parasites-can-make-you-reckless-213177

http://www.citybengaluru.com/promiscuous-parasites-can-make-you-reckless/

http://www.indiatalkies.com/2011/09/promiscuous-parasites-reckless.html

Amwayagent

http://www.amwayagent.com/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells.html

InfectionControlToday

http://www.infectioncontroltoday.com/news/2011/09/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells.aspx

ScienceDaily

http://www.sciencedaily.com/releases/2011/09/110921120056.htm

NewsWise

http://www.newswise.com/articles/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells

Science Codex

http://www.sciencecodex.com/researchers_discover_how_promiscuous_parasites_hijack_host_immune_cells

MedicalNewsToday

http://www.medicalnewstoday.com/releases/234798.php

NewsBlaze

http://newsblaze.com/story/2011092108200300003.wi/topstory.html

RedOrbit

http://www.redorbit.com/news/science/1112386702/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells

New York Ag

http://www.newyorkagconnection.com/story-state.php?Id=835&yr=2011

Biocompare

http://news.biocompare.com/News/NewsStory/394349/Researchers-Discover-How-promiscuous-Parasites-Hijack-Host-Immune-Cells.html

Science Newsline

http://www.sciencenewsline.com/biology/2011092117140007.html

Sify News

http://www.sify.com/news/promiscuous-parasites-can-make-you-reckless-news-international-ljwpuqjjiei.html

News Medical

http://www.news-medical.net/news/20110922/Cornell-researchers-identify-how-T-gondii-controls-hosts-immune-system.aspx

http://happinessbeyondthought.blogspot.com/2011/09/brain-parasite-in-most-of-us-prompts.html

Viral quality controls could halt herpes’ spread

Sept. 13, 2011

Herpesviruses are thrifty reproducers — they only send off their most infectious progeny to invade new cells. Two Cornell virologists recently have discovered how these viruses determine which progeny to release.

herpes simplex virion

Recently enveloped herpes simplex virion in the perinuclear space of an infected cell.

The College of Veterinary Medicine researchers report in the Aug. 23 (108:34) issue I of the Proceedings of the National Academy of Sciences on the mechanisms of this quality-control system, which helps streamline viral reproduction to optimize its spreading.

The virologists identified proteins in the nuclear membranes of infected cells that control which viral products exit. This map could be used to identify new targets for future drugs that would hamper viral reproduction by clogging inspection pathways to trap viruses in the cells they first infect.

“When a herpesvirus hijacks a cell, it turns the nucleus into a viral production factory,” said Joel Baines, the James Law Professor of Virology, who co-authored the study with postdoctoral research associate Kui Yang. “It makes protein shells called capsids, stuffs them with viral DNA and ships them out of the nuclear membrane to infect new cells. But errors in the assembly line leave some capsids empty, without DNA, and shipping these is a waste of resources.”

When capsids bud from the nuclear membrane, they take pieces of it with them, forming protective lipid envelopes that let them move to new cells. Empty capsids can’t reproduce, so the virus only allows capsids with DNA through. How the membrane could determine whether the capsid had DNA or not was a mystery until Yang and Baines mapped its method.

Joel Baines

Joel Baines

“We found clamplike proteins on the surface of herpesvirus capsids that hold them together and keep them from bursting when they’re stuffed full of DNA,” said Baines. “Those with DNA have far more of these than empty capsids. We also found a protein complex living in the host cell’s nuclear membrane that binds to these structural support proteins, selecting DNA-filled capsids to pull through the membrane. Thus the virus releases only its most infectious particles.”

This streamlining process has helped herpesvirus species spread prevalently and permanently across all animal species. Eight of the 25 known viruses in the herpes family regularly infect humans, posing a leading cause of human viral infection.

Once in a body, herpesvirus stays for life. It can flare up at any time, causing symptoms and diseases, ranging from infected sores to brain inflammation, birth defects and cancers of the nose, throat and lymphatic system. Though usually not fatal, herpes can prove dangerous to patients with weak immune systems, such as those with HIV/AIDS or infants who contract HIV/AIDS from their mothers.

Various species of Herpesvirus

Various species of Herpesvirus

There is no cure for herpes, but Baines’ map illustrates a viral reproduction system that can be subverted.

“Take away either component, the capsid’s clamplike proteins or the membrane’s inspector proteins, and nothing escapes the host cell,” said Baines. “This opens the door to developing drugs that could block the interactions between these protein complexes, covering the binding sites to clog the system so that no viral particles get through. This would significantly slow or even stop the virus’s spread between cells. Our lab is now working on even more detailed maps of these proteins’ exact interaction sites that will help drug developers pinpoint precise targets to thwart viral reproduction.”

The research was supported, in part, by the National Institutes of Health.

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

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Original press release:

Cornell University College of Veterinary Medicine news
http://www.vet.cornell.edu/news/herpes.cfm

Media hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Sept11/HerpesMap.html

MyScience

http://www.myscience.cc/wire/discovery_could_lead_to_ways_to_halt_spread_of_herpesvirus-2011-cornell

Bionity

http://www.bionity.com/en/news/134351/study-uncovers-how-herpesvirus-spreads.html?WT.mc_id=ca0067

MedicalXPress (PhysOrg)

http://medicalxpress.com/news/2011-09-discovery-ways-herpes.html

Electronic Component News

http://www.ecnmag.com/News/Feeds/2011/09/blogs-the-cutting-edge-discovery-could-lead-ways-to-prevent-herpes-spread/

Futurity

http://www.futurity.org/health-medicine/how-to-stop-herpes-from-going-viral/

Herpes Pain Relief

http://www.herpespainrelief.info/4349/cornell-chronicle-study-uncovers-how-herpesvirus-spreads/