How can fat help fight infection?

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New research is shedding light on the mechanisms by which our bodies can use fat to fight infections. VICTOR TORRES / Stocksy
  • Salmonella infection causes 420 deaths in the United States each year, and it is the leading cause of blood infection in Africa.
  • The infection is linked to increased hematopoietic stem cell (HSC) activity and the production of white blood cells.
  • A series of new experiments identify how resting HSCs help produce mature white blood cells.
  • Mouse hematopoietic stem cells with a Salmonella Typhimurium the infection contained more fatty acids than those without infection.
  • An increase in the CD36 protein (a surface receptor) has been associated with S. typhimurium infection.
  • Additional CD36 receptors facilitated the absorption of free fatty acids to activate HSCs and provide an energy source.

According to Centers for Disease Control and Prevention (CDC), 1.35 million people contract Salmonella infection each year in the United States, resulting in 26,500 hospitalizations and 420 deaths.

The CDC believes that food contaminated with fecal matter transmits 94% of Salmonella infections. Drinking contaminated water and touching contaminated animals can also cause infection. Symptoms include nausea, vomiting, abdominal cramps, diarrhea, and sepsis.

S. typhimurium causes the majority of non-typhoidal salmonella infections and is the leading cause of blood infection (sepsis) in Africa, associated with death rate of 20 to 25%.

The infection causes an increase in the number of hematopoietic stem cells (HSC) in the bone marrow.

HSCs are responsible for hematopoiesis, a process that forms all types of blood cells: platelets, red blood cells, and white blood cells to help the body fight infection. Scientists do not fully understand how the infection causes hematopoiesis.

HSCs are usually inactive, but when infected they react quickly, increasing the number of white blood cells. Studies have shown that activated HSCs use free fatty acids in the body’s fat stores for energy to respond to infection.

Fatty acids are the building blocks of fat in our body. All fats play an important role in the body, but some fats are better than others for long term health. Some research has linked the infection to an increase in free fatty acids in the blood.

A study led by Dr Stuart Rushworth, Associate Professor, Norwich Medical School, University of East Anglia, UK, demonstrated higher levels of free fatty acids in the blood of mice 72 hours after infection with S. typhimurium.

The study – published in nature communication – demonstrates the activity of HSCs in mice infected with S. typhimurium. The number of HSCs increased 72 hours after infection and contained more fat than the HSCs from uninfected mice.

The results suggest that HSCs can use free fatty acids to generate energy to support increased cellular activity during bacterial infection.

“Fighting infections takes a lot of energy, and fat stores are huge energy stores, which provide fuel to blood stem cells to boost the immune response,” notes Dr Rushworth.

CD36 is a protein present on the surface of HSCs which displaces free fatty acids inside the cell. Once inside the cell, they travel to its “powerhouse”, the mitochondria, where the cell uses free fatty acids for energy.

In the study, researchers pretreated mice with a CD36 inhibitor before infecting them with S. typhimurium. HSCs from CD36 inhibited mice had lower free fatty acid levels and activity levels and could not increase the number of cells needed to respond to infection.

Postdoctoral Fellow Dr Jayna Mistry tweeted: “We show Salmonella infection results in the uptake of fatty acids by HSCs, an essential process in the immune response to infection.

Speaking about the future of work, Dr Rushworth said: “I hope our findings will help improve the treatment of vulnerable and elderly people with infections by boosting their immune response.

Research is helping to better understand how HSCs behave in the bone marrow as the body fights infections, which may also lead to alternative treatments for bacterial infections.

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