A recent study has shown that deletion of a protein in white blood cells improves their ability to
eradicate infections with the bacteria Staphylococcus
aureus (S. aureus), although not the fungus Aspergillus
fumigatus (A. fumigatus), in an animal model of
chronic granulomatous disease (CGD).
CGD is a disorder that causes the immune system to
malfunction, resulting in a form of immunodeiciency.
Individuals with CGD have recurrent bacterial and
fungal infections, and often have areas of inlammation
(granulomas) in various tissues that can cause damage.
The body’s white blood cells normally eliminate bacteria
via two modes of action—a non-oxidative mode of
action that involves the use of specialized enzymes to
attack and cleave proteins that are necessary for bacterial
survival, and an oxidative mode involving chemically
reactive molecules containing oxygen. It is the oxidative
mode of defense that is defective in patients with CGD.
Building on their previous research indings showing
that a protein called “olfactomedin-4” (Olfm4) hinders
white blood cells’ ability to eradicate bacteria, the
researchers deleted the Olfm4 gene in a mouse model
of CGD and evaluated the impact of this deletion on
host defense against S. aureus and A. fumigatus, both
of which are common causes of infections in people
with CGD. White blood cells obtained from mice
lacking Olfm4 protein showed increased ability to kill
S. aureus compared to white blood cells having Olfm4.
Likewise, when mice lacking Olfm4 were exposed to
S. aureus for six hours, they killed signiicantly more
bacteria than mice with Olfm4.
Next, the investigators examined whether deletion of
Olfm4 in CGD mice enhanced host defense against
infections of S. aureus and A. fumigatus as measured by
survival over a two week testing period. When infected
with S. aureus, all CGD mice with Olfm4 died within
ive days, while the majority (approximately 85 percent)
of CGD mice without Olfm4 survived the two-week
testing period. Notably, approximately 75 percent of
normal mice with Olfm4 died within eight days. When
infected with A. fumigatus, all CGD mice died within
nine days, whether or not they had Olfm4. In contrast,
all normal mice with or without Olfm4 survived the two
week testing period following A. fumigatus infection.
These results show that Olfm4 deletion can enhance host
defense against S. aureus, but not A. fumigatus, in CGD
mice. Future studies are needed to determine the role of
Olfm4 in human white blood cells and could lead to the
development of a therapeutic inhibitor of Olfm4 activity
to boost human defense against infection.
Liu W, Yan M, Sugui JA et al. Olfm4 deletion enhances
defense against Staphylococcus aureus in chronic
granulomatous disease. J Clin Invest 123: 3751-3755, 2013.