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."

TITLE: HIF-1alpha expression regulates the bactericidal capacity of phagocytes

AUTHOR CONTACT:
Randall Johnson
University of California, San Diego, La Jolla, CA USA
Phone: 858-822-0509; E-mail: rsjohnson@ucsd.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=23865

ACCOMPANYING COMMENTARY:

Title: HIF-1alpha: a master regulator of innate host defenses?

AUTHOR CONTACT:
Harry L. Malech
NIAID, National Institutes Of Health, Bethesda, MD USA
Phone: 301-480-6916; Fax: 301-402-0789; E-mail: hmalech@nih.gov

View the PDF of this article at: https://www.the-jci.org/article.php?id=25740