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.com
Volume 6
Journal of Infectious Diseases and Therapy
ISSN: 2332-0877
Infection Congress 2018
March 01-02, 2018
March 01-02, 2018 Berlin, Germany
5
th
International Congress on
INFECTIOUS DISEASES
J Infect Dis Ther 2018, Volume 6
DOI: 10.4172/2332-0877-C1-039
Role of the hepcidin-ferroportin axis in controlling the iron content of the cytosol and
Salmonella
-
containing vacuoles in infected macrophages
Hyon Choy
Chonnam National University, South Korea
I
ron plays a dual-role in bacterial infection: first, it is a critical micronutrient required for the proliferation of infecting
bacteria, and second, it acts as a cofactor in the generation of bactericidal free radicals. Macrophages provide a major source
of serum iron by releasing cytoplasmic iron via the membrane bound iron export protein, ferroportin (FPN), degradation of
which is triggered by hepcidin produced by hepatocytes upon bacterial infection.
Salmonella typhimurium
is an intracellular
pathogen capable of invading macrophages and proliferating in the membranous
Salmonella
-containing vacuole (SCV). In
this study, we first demonstrate that FPN is localized on the SCV and plays a role in iron transport into the SCV. To measure
iron content in the SCV, a biosensor was constructed by fusing the iron responsive iroB promoter of
Salmonella
to a mutant
GFP with a short half-life (gfpOVA). Using this construct, we estimated the iron levels in macrophages in animals as well as
in in vitro cultured macrophages in the presence and absence of hepcidin. In contrast to the generally accepted opinion, the
iron level in the SCV in the presence of the iron transporter (FPN) was higher than in its absence (+hepcidin). In general,
host defense against pathogens relies on the generation of reactive oxygen species (ROS) in phagocytic cells, especially during
the early stage of infection. Thus, we examined for the generation of bactericidal ROS in the SCV using another biosensor
composed of the ROS-responsive katG promoter of
Salmonella
fused to gfpOVA. To our surprise, ROS generation in the SCV
was higher in the presence of FPN than in its absence. The relatively high level of iron in the SCV increased the generation of
bactericidal ROS, which in turn decreased the number of intra-macrophage
Salmonella
and extended infected animal survival.
Thus, this study reveals the mechanism via which a block in the hepcidin-FPN circuit controls intra-macrophage
Salmonella
infection
.
hyonchoy@jnu.ac.kr