Georgetown biology professor discovers redundancy in intestinal immune system

Steven SingerLast Wednesday, a study published in the online journal mBio by biology department chair Steven Singer, pictured at left, and his team shows novel effects of two genes that counteract the effects of Giardia duodenalis, the most common cause of parasitic diarrhea in the world. The study also describes the strong antibody response launched in mice and humans in the presence of Giardia infection, although the paper also shows that the antibodies are not needed in order to effectively combat an acute case of Giardia.

Singer and his team were the first to effectively manipulate the genetics of the parasite. His study focused specifically on the genes Mmp7 and Nos2. Proteins produced by the gene Mmp7 can effectively kill Giardia in test tube trials. Nos2, a gene that leads to the production of nitrous oxide, was shown to play a role in preventing the growth of Giardia in parasite cultures. A knockout of both of these genes simultaneously in live animals led to animals with a greater susceptibility to the effects of Giardia. A knockout of one of these genes, while leaving the other intact in the genome, showed almost no effect on the susceptibility of live animals to Giardia. This implies that our immune response to this parasite has a redundancy built in; both genes can effectively cause an immune response to limit the spread of Giardia.

“Our findings suggest that the function of these genes are redundant – either one could help eradicate the infection, so while blocking either one had little effect, blocking both was much more dramatic.” Singer said. “This research brings us one step closer to understanding the best mechanisms to control this pervasive infection,”

The immune response to Giardia is one of the rare instances of immunologic redundancy in the human body. The human body has multiple lines of defense against pathogens in the environment. Giardia itself is an infection of interest, due to the lethal effects of diarrhea and subsequent dehydration in children throughout many impoverished countries.

Singer was joined in this study by Erqui Li, associate research professor of biology, Ernest Tako (G’08) and Maryam Farzad Hassimi (G’01), of the Sloan-Kettering Institute.

PhotoGeorgetown University

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