June 30, 2005
Eliminating Bacterial Infections Out of Thin Air
When microorganisms invade the body, immune mechanisms kick in to fight them off. The infected tissues typically show depleted oxygen levels, and a protein called HIF-1 alpha regulates this. Interestingly, the cells responsible for destroying the foreign pathogens are effective in this low-oxygen environment. In a new study appearing in the July 1 print issue of The Journal of Clinical Investigation, Randall Johnson and collegues from UCSD show for the first time that induction of the HIF-1 pathway can act as a "super-antibiotic", accelerating the killing of bacteria in conditions typical of those found during bacterial infection and sepsis.
The authors show that regulation of HIF-1 is required for immune defense against bacterial infection. They also show that bacteria killing is increased under conditions of low oxygen due to HIF-1 upregulation, and that bacterial infection upregulates HIF-1. In fact, upregulation of HIF-1 enhances expression of bactericidal agents and killing of bacteria.
This reveals that a novel approach to treating bacterial infection is by increasing the killing capacity of cells of the innate immune system. In a related commentary, Kol Zarember and Harry Melach write, "By dissecting the role of HIF-1 in innate immune defenses, the study"¦introduces new targets for therapeutic immunomodulation."
On the Web: