Dr. Iwasaki is also a Waldemar Von Zedtwitz Professor of Immunobiology, and of Molecular Cellular, and Developmental Biology at Yale University.
Antiviral Immune Defense Mechanisms
An immunology class at the University of Toronto changed Akiko Iwasaki's life. She had traveled to Canada after high school in her native Japan with hopes of becoming a mathematician or a physicist like her father.
"I knew that my potential would be greater if I left Japan," she says. Women there, she explains, are expected to marry, have children, and quit working. "I knew that wasn't for me." The undergraduate course opened up new possibilities. "I had never been taught a subject in biology that was so relevant to human health," she says. "I fell in love with immunology."
She chose to pursue a PhD project probing how vaccines made from bits of DNA elicit an immune response. Because these DNA vaccines work best when injected into muscle, scientists thought that muscle cells were crucial for alerting the immune system to the foreign proteins, or antigens, coded for by the vaccines. Wrong. In the first of a number of discoveries Iwasaki has made that both reveal fundamental biological mechanisms and point the way to advances in human health, she was among the first to show that the antigen-presenting cells were in the blood, not muscle. She upended the view of DNA vaccines. "It did cause a big stir," she recalls.
Iwasaki then turned her attention to the front lines of the battleground between people and pathogens—the mucosal surfaces that line the gut and genital tract, where many viruses and bacteria gain entry. As a postdoctoral fellow at the National Institutes of Health, she painstakingly extracted dendritic cells from lymph nodes called Peyer's patches in the mouse gut and discovered that dendritic cells send signals that tell the immune system whether incoming antigens are benign like food or dangerous like Salmonella bacteria. Once she started her own lab at Yale University in 2000, she focused on the genital mucosa, about which hardly anything was known, and continued to break new ground.
Iwasaki focused on the crucial role of dendritic cells in recognizing viral invaders. She identified receptors on those cells that recognize viruses and discovered the importance of autophagy (a process in which cells destroy unwanted material inside themselves) in how dendritic cells respond to pathogens. She also realized that some standard vaccines have a serious limitation. Yes, they can prod the immune system to make antibodies and to prepare T cells that attack invaders in the blood. Unfortunately, however, the T cells don't migrate to the genital tract, creating an ideal environment for opportunistic viruses like herpes simplex virus that can easily gain entry and cause infection. "We came to realize T cells must be present in the mucosa to protect the host," Iwasaki says.
So she devised a new strategy to create that crucial first line of defense. First, prime the immune system with a standard vaccine. Then apply a cell-attracting chemical, or chemokine, to the genital tract to pull T cells into the area. "Simply doing that once recruits the T cells, and somewhat miraculously, the T cells stay," she says.
This "prime-and-pull" approach prevents genital herpes in mice and cures them of the disease. "We are great mouse doctors," Iwasaki laughs. She is collaborating with several companies on preventive and therapeutic vaccines for genital herpes that will work in humans. And she's planning to test prime-and-pull vaccination against HIV, where infection happens too quickly for T cells circulating in the blood to subdue the virus. "We're hoping to set up the defense right at the border," says Iwasaki.