Print Version

DMS Receives $7.2 Million Grant to Study New Ways to Tackle Infections

Hanover, NH - Dartmouth Medical School researchers are exploring the role sex hormones play in the body's rapid response protection system through a National Institutes of Health grant for collaboration that could lead to new approaches to combat infections and autoimmune diseases.

The National Institute of Allergy and Infectious Diseases has awarded DMS $7.2 million for an array of studies that traverse immunology, physiology and obstetrics/gynecology in a five-year program project headed by Charles Wira, PhD, professor of physiology.

This new, comprehensive program focuses on a facet of the immune system called innate immunity, the first line of defense when bacteria or viruses invade the body. The innate response kicks in immediately to eradicate or reduce the potential infection.

In contrast, adaptive, or acquired, immunity occurs gradually with antibodies and T cells that encounter microbes and attack them, then set up the body to trigger an immune response on subsequent exposure. Only recently have researchers begun to appreciate the power of the innate immune system in humans.

Drawing on the talents of immunologists and endocrinologists, four DMS teams are scrutinizing the essential blood and epithelial cells of the innate immune system to define how the sex hormones � androgens, estrogens and progestins � shape the innate function in women and men. Collectively, they aim to understand how the innate and adaptive systems communicate, and if the early warning innate system can turn on an adaptive response. The work is expected to shed light on preventing and treating infections, including HIV and other sexually transmitted diseases, autoimmune disorders and gynecological cancers.

"The innate immune system is constitutive; it's always there," says Wira. "We're interested in seeing if it is in fact regulated by hormones and whether differences between men and women influence this protection. The cells we're studying are all key players in the innate system; they are immediately challenged and if they do their job completely, then the body doesn't initiate an immune response. But, if that level of protection is not sufficient, then they play an important role in stimulating the adaptive system to bring on this whole other level."

The work builds on a prior program project, which Wira also headed, on women's reproductive health and immunity that has revealed some intriguing clues to disease susceptibility and treatment potential. Recent work by John Fahey, PhD, and Wira, for example, has shown that the cells lining the uterus secrete a bacteria-killing molecule, whose activity is present during the menstrual cycle and is inactive in post menopausal women. "The message," says Wira, "is that that within the innate immune system, there are endogenous microbicides, which if they could be turned on, might lead to prevention of infection on conditions of exposure to a potential pathogen."

The four projects and the leaders are:

• The influence of female sex hormones on the epithelial cells that line the mucosal surface of the female reproductive tract: Wira and Fahey, research assistant professor of physiology
  
  
• The effect of gender and steroid sex hormones on the function of blood cells called polymorphonuclear neutrophils, a critical element of the innate immune system: Paul Guyre, PhD, professor of physiology.
  
  
• The role of sex hormones on myeloid cells - the macrophages and dendritic cells, which are rapid effectors of innate immunity and are also involved in the adaptive response: Michael Fanger, PhD, professor of microbiology and immunology.
  
  
• The regulation of natural killer cells by androgens and estrogens in men and women, as well as how these cells are programmed to act in the female reproductive tract: Charles Sentman, PhD, assistant professor of microbiology and immunology.