Science Advances: Iron deficiency suppresses important functions of the innate immune system

There are two proteins that ensure that cells absorb iron
when they need it.
If both control proteins were turned off in mice, the animal would develop severe anemia
as expected.
Surprisingly, at the same time, one cell type of innate immune defense, neutrophils, also decreased dramatically, as
scientists at the German Cancer Research Center demonstrated for the first time.
Iron deficiency, a known defense mechanism against infectious agents, is a double-edged sword because it simultaneously suppresses the defenses of an important arm of the innate immune system
.

A balanced iron metabolism is a necessary prerequisite for
our health.
Drugs that target iron deficiency or iron overdose are one of the most widely prescribed therapies in the
world.
The fact that iron is an indispensable component in the blood is almost well known: this metal is an important component of hemoglobin, responsible for transporting oxygen
in red blood cells.

The iron supply to the cells is controlled
by two proteins, IRP-1 and IRP-2.
If the cell is iron deficient, IRP-1 and IRP-2 accelerate the production of various iron transporters that bring iron into the cell
.
IRP-1 and IRP-2 also ensure that the same dangerous iron excess does not occur
.

IRP-1 and IRP-2 are critical for survival: Mice that lack these two control proteins during embryonic development die
in utero.
But what happens when IRP-1 and IRP-2 fail in adult mice? A team led by Bruno Galy of DKFZ has now conducted research
in mice that can stop IRP production after injecting the drug.

As the researchers expected, the most significant change after the IRP was turned off was a significant decrease
in red blood cells.
Due to the lack of hemoglobin, these red blood cells can only reach the smallest size
.

However, the researchers were surprised to find that white blood cells also decreased
dramatically.
Further examination revealed that this decline was mainly due to a lack of neutrophils
.
These immune cells make up two-thirds of the body's white blood cells and are an important part
of the innate immune system.

This decline is not caused by the mass death of neutrophils, but by developmental blocks in the hematopoietic system: precursor cells in the bone marrow no longer develop into mature neutrophils because this differentiation process is apparently dependent on iron
.
Other types of white blood cells, such as monocytes, are not affected by IRP-dependent developmental blockade
.

The limits of iron are a double-edged sword

"The strong dependence of neutrophils on iron was previously unknown
.
It may affect immune defenses against bacterial pathogens," Bruno Gurry said
.
Interestingly, on the other hand, iron deficiency is one of the body's defense strategies in the event of a bacterial infection: many pathogens rely on iron
.
To slow down their reproduction, the body stores metals in certain cells as a storage chamber, making it harder for pathogens to access this valuable resource
.

Another paper published in the same issue of the journal Science Advances* (in which Galy was also involved) showed that iron deficiency in the serum (which usually occurs at the time of infection) causes neutropenia in mice and limits the ability of these immune cells to
fight bacteria.
"Iron deficiency obviously regulates the innate immune system
.
It inhibits the maturation of neutrophils, as well as their defenses," Bruno Galy said, adding: "The limitation of available iron is obviously a double-edged sword: on the one hand, the body thus stops the spread
of bacteria.
" On the other hand, the function of an important branch of the innate immune system is affected
.
”

Not only infections, inflammation also often leads to iron deficiency, which leads to anemia
.
As a result, cancer patients with chronic inflammation are often affected by anemia, which can severely limit their quality of
life.
"Next, we want to investigate whether iron deficiency in chronic inflammation also impairs immune function," Gary said
.