Published April 17, 2013 | On the Pulse
Researchers at Seattle Children's Research of Insitute, a member of WGHA, have uncovered a surprising new role for one type of immune cell in controlling Trypanosoma cruzi, a parasite that causes an infection known as Chagas disease
. The disease, classified as a Neglected Tropical Disease
by the Centers for Disease Control and Prevention, is found mainly in Latin American countries and is a potentially life-threatening illness that can lead to heart and other health issues. There is no cure for Chagas disease, and an estimated eight million people
are infected worldwide, according to the World Health Organization.
The study was published
April 7 in Nature Immunology
David Rawlings, MD
, of Seattle Children’s Research Institute, said the study shows for the first time that in response to Trypanosoma cruzi, B cells (immune cells best known for making antibodies) produce an inflammatory protein called Interleukin (IL)-17. “It’s not only a new way of thinking about how this parasite is controlled, but it also gives us new clues about how B cells work,” he said.
IL-17 increases inflammation by causing cells to release more pro-inflammatory substances.
Rawlings first met Adriana Gruppi, PhD, of the National University of Cordoba, when she visited Seattle more than five years ago. They struck up a conversation about her work on Trypanosoma cruzi. “We talked about B cells, which I study in my lab, and I became interested in the role B cells potentially played with this parasitic disease,” Rawlings said. The international study is a culmination of a five-year collaboration, which included several visits over the years to Rawlings’ lab from Argentine counterparts.
IL-17 role in immune diseases
IL-17 plays an important role in immune diseases. Specifically, the dysregulation of IL-17 made by other cell types (not B cells) has been found to play a crucial role in auto-immunity, including in multiple sclerosis. “Researchers have long thought that the main cells that made IL-17 were T cells and some other cell types similar to T cells,” said Rawlings.
One of the most effective ways to treat auto-immune diseases, including diabetes, multiple sclerosis, and rheumatoid arthritis, is to eliminate B cells. “One key implication of our work is since B cells can clearly make IL-17, when we treat people with therapies that get rid of B cells, these therapies might be helping by removing B cells making IL-17.”
Rawlings and the team will follow up on these findings to determine whether B cells make IL-17 in various auto-immune diseases as well as in other types of infections. The researchers also plan to follow up on what signals activate this whole process, since B cells use pathways that are totally distinct from IL-17 production by other cell types.
“There’s interesting potential for follow-up because there are other, much more common infections—including pneumococcus—that make an enzyme similar to the one made by Trypanosoma cruzi that initiates this process,” he said. Pneumococcus is the most common cause of bacterial pneumonia and is associated with meningitis and other infectious diseases.
Rawlings’ background includes a stint as a research fellow studying parasitic diseases, including malaria, at the National Institutes of Health. This study was conducted looking at both mouse and human primary B cells.
Rawlings is also a professor of pediatrics and adjunct professor in the Department of Immunology at the University of Washington School of Medicine. Co-authors on the study include Mohamed Oukka, PhD; Shaun Jackson, MD, PhD; Blythe Sather, PhD; Akilesh Singh, PhD; Socheath Kim (Seattle Children’s Research Institute, University of Washington); Denny Liggitt, DVM, PhD (University of Washington); Daniela Bermejo, Adriana Gruppi, Melisa Gorosito-Serran, Eva Acosta-Rodriguez, Maria Amezcua-Vesely (National University of Cordoba), Juan Mucci and Oscar Campetella(National University of San Martin).