MIT researchers study Toxoplasma protein discovery for anti-inflammatory potential

CAMBRIDGE, Mass.—Researchers at the Massachusetts Instituteof Technology (MIT) have recently released a paper following the discovery thata protein in a strain of a common parasite, Toxoplasmagondii, is capable of suppressing inflammation in an infected host, whichcould help researchers to learn how to turn off inflammation in patientssuffering not just from the parasite but from other inflammatory diseases aswell.

The parasite Toxoplasmainfects about one-third of the world's population, and over 60 million peoplein the United States alone carry the parasite, according to Medline Plus of theNational Library of Medicine. It can be contracted from dirt, raw meat,unwashed fruits or vegetables, infected water or feline waste. Toxoplasma comes in several strains,though the type II strain, which is the most common type in North America andEurope, is the strain most often found in patients who experience complicationsfrom the parasite. Types I and III are generally found less often than type IIin patients with Toxoplasma symptoms.Some people infected with Toxoplasmacan display serious symptoms such as encephalitis, inflammation of the brainthat can lead to bleeding as well as brain damage, while some display nonoticeable symptoms at all.

That paradox is one that Jeroen Saeij, an MIT biologist,assistant professor of biology and corresponding author of the paper, ispursuing. Saeij has been studying Toxoplasmafor years, and his latest work led him to the discovery that two of the threemost common strains of the parasite actually suppress inflammation. Given howmany people suffer from inflammatory diseases—which include Crohn's disease,Alzheimer's, Parkinson's, asthma, hepatitis, rheumatoid arthritis andinflammatory bowel diseases such as ulcerative colitis—being able to isolateand reproduce Toxoplasma's ability tosuppress inflammation could have widespread applications.

"There's a lot of these inflammatory diseases, and ifthere's a general pathway that's really good at quelling inflammation, theremight be [drug] applications," said Saeij in a press release about the paper.

The paper, entitled "ToxoplasmaPolymorphic Effectors Determine Macrophage Polarization and IntestinalInflammation," was published in the June 15 issue of Cell Host & Microbe. The lead author of the paper ispost-doctorate Kirk Jensen.

Saeij's previous work with colleagues had demonstrated thatthe type II strain, which results in the most symptoms for sufferers, of Toxoplasma produces the protein GRA15,which causes inflammation. The newest work has shown that the type II strainalso produces a variant form of another protein, ROP16. While ROP16 suppressesinflammation in the host in types I and III, the protein has no such effect inthe type II strain. However, when the researchers inserted ROP16 from type Iinto a type II strain, the protein suppressed inflammation in that strain aswell. Toxoplasma infection in mice wasstudied for the experiment, and the resulting inflammation of the intestineclosely resembles that of patients suffering from Crohn's disease, whichaffects approximately half a million U.S. citizens.

The differences in Toxoplasma'sstrains are due to the parasite evolving to take advantage of the differentimmune reactions of potential hosts. The parasite promotes some level ofinflammation so that the host can survive other serious infections, which allowit to survive and form tissue cysts to spread to other victims. But since toomuch inflammation can kill the host, the adaptation of the strains allows theparasite to survive in a variety of hosts.

The next step for Jensen and Saeij is to further study ROP16in hopes of pinpointing how the protein induces its anti-inflammatory effects,as they could hold the potential for new drugs. Saeij cautions that suchdevelopments, however, are years away.

"In reality, going from a discovery to a drug can takedecades," he says. "You hope that you contribute to something like that, butthat's always a long road."

The paper's authors include, in addition to Jensen andSaeij, Kenneth Hu from MIT; Elia D. Tait Wojno and Christopher Hunter from theDepartment of Pathobiology at the University of Pennsylvania; Anjali Shastri,Yi-Ching Ong, Yueh-hsiu Chlen and John Boothroyd from the Department ofMicrobiology and Immunology at Stanford University; Yiding Wan from MIT and the Departmentof Microbiology at the Wageningen University and Research Centre in theNetherlands; Lara Cornel from MIT and the Department of Cell Biology andImmunology at the Wageningen University and Research Centre; and Erwan Boedecfrom MIT and the Strasbourg School of Biotechnology in France.