Cytokine interference in infection
Dr. O’Garra’s laboratory studies cells and molecules that control our immune systems to understand how they respond to infections and influence the outcomes and what goes wrong when infections damage healthy cells. For example, some infected individuals are protected while others go on to progress to disease such as tuberculosis (TB), which is caused by infection with Mycobacterium tuberculosis (M. tuberculosis). TB is a major cause of morbidity and mortality worldwide and efforts to control this disease are hampered by difficulties with diagnosis, prevention, and treatment. Most people infected with M. tuberculosis remain asymptomatic or have latent (noninfectious) TB, but they have a 10 percent lifetime risk of developing the active form of the disease. In 2010, Dr. O’Garra’s laboratory identified a gene signature dominated by type I interferon (IFN) inducible genes in the bloodstream of people with TB, which disappears during successful treatment. The lab is also studying the regulation and function of type I IFNs which exacerbate bacterial infections, in part, by inducing a regulatory cytokine called IL-10. Type I IFNs are cytokines that have been shown for years to be important in the control of viral infections. In experimental models, the lab showed that elevated levels of this cytokine lead to increased TB disease; subsequent studies now provide further knowledge regarding the heterogeneity of this blood signature in some, but not all, asymptomatic TB contacts and how this signature relates to whether they are protected or will develop the disease. During the lecture, Dr. O’Garra will discuss several potential mechanisms underlying the contribution of type I IFN to the development of TB and diseases caused by other bacterial infections. She will also discuss the impairment of protective responses.
Med. 30-60 min