Researchers have shown how the human body fights back in response to Salmonella infections. Their work has shown that blood stem cells respond in the first few hours following infection by acquiring energy from bone marrow support cells.
It is hoped the findings, published in the journal PNAS, could help new approaches to treat people with Salmonella and other bacterial illnesses.
A team from the University of East Anglia, with Norwich Research Park colleagues at the Norfolk and Norwich University Hospital (NNUH), the Quadram Institute and Earlham Institute (EI), to study mitochondria – that live inside cells and give them energy.
They used Salmonella typhimurium and its outer membrane lipopolysaccharide (LPS) to model acute bacterial infection.
Treating weak immune systems
Lead researcher Dr. Stuart Rushworth from UEA’s Norwich Medical School, said Salmonella is one of the most common causes of food poisoning worldwide.
“Most people recover without treatment but young children, the elderly and people who have immune systems that are not working properly have a greater risk of becoming severely ill and it can be deadly. We wanted to find out how the immune system responds to Salmonella bacterial infection. Knowing more about how our bodies respond could help develop new ways to treat people with weak immune systems, such as the elderly,” Rushworth said.
Scientists analyzed the immune response to Salmonella bacterial infection, by using blood and bone marrow cells donated for research by NNUH patients. They worked with Salmonella infection experts from Quadram to study the way mitochondria moves between different cell types, using microscopes and DNA analysis.
The team found that in the bone marrow where blood cells are made, support or stromal cells were forced to transfer their power-generating mitochondria to neighboring blood stem cells. Mitochondria are transferred to blood stem cells within two hours of sensing infection. Leukocytes are required for the immune system to respond to bacterial infection. If mitochondrial transfer is blocked, an increase in bacterial colonization occurs.
“We found that these support cells were effectively charging the stem cells and enabling them to make millions more bacteria-fighting white blood cells,” said Rushworth.
“It was not previously known how blood stem cells acquire the energy they need to mount an immune response to infection. Mitochondria are like tiny batteries which power cells. In response to infection, the immune system takes mitochondria from surrounding support cells to power up the immune response.”
Results provide insight into how the blood and immune system is able to respond quickly to infection.
“Working out the mechanism through which this power boost works gives us new ideas on how to strengthen the body’s fight against infection in the future. This work could help inform how older people with infection might be treated. It is an essential first step towards exploiting this biological function therapeutically in the future,” said Rushworth.
Restrict magnesium to stop growth
Meanwhile, researchers from the University of Basel in Switzerland have found a shortage of magnesium stops pathogen growth.
Olivier Cunrath and Profressor Dirk Bumann at the Biozentrum, University of Basel, found that magnesium is crucial for bacterial growth inside host cells. Magnesium starvation is a stress factor for the bacteria, which stops their growth and replication. The host cells limit magnesium supply to these intracellular pathogens using a transport protein called NRAMP1.
Researchers investigated Salmonella, a bacterial pathogen that causes gastroenteritis. Whether and how quickly Salmonella replicate and spread depends on the functioning of the NRAMP1 transporter. Results have been published in the journal Science.
Findings could help to develop drugs that would make it harder for the bacteria to get magnesium and further slowdown the pathogens to give the host an advantage in defeating the infection.
“Magnesium seems to be the Achilles heel for intracellular pathogens. The less magnesium is available, the harder they try to get it. The bacteria go on alert and activate all magnesium uptake systems. However, if the pump in the host cells is defective, magnesium is available in sufficient quantities to enable rapid Salmonella growth,” said Cunrath.
Macrophages are a first line of defense against pathogenic bacteria like Salmonella. These immune cells possess a metal-ion transporter called SLC11A1 or NRAMP1, which is involved in infection resistance.
Humans with reduced NRAMP1 are more susceptible to various intracellular pathogens. If this transporter is absent, even a very small number of pathogens can cause a fatal infection.
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