“More research is needed to better understand this process and develop better, and much needed, therapeutic strategies for sepsis,” said Nadia Carlesso, MD, PhD from the Indiana University School of Medicine.
In a unique study that focused on the early stages of acute infection rather that late stages of sepsis, researchers looked at the molecular signaling system in mice models of sepsis thought to be responsible for suppression of key cells. If scientists can determine if the acute infection stage is where the system starts to err, intervention at this stage could potentially prevent a severe septic response from occurring in the body.
First, the researchers discovered the details of the relationship between immune cells, hematopoietic stem cells, and the molecular signaling system during sepsis. For whatever reason, errors in signaling led to hematopoietic stem cells failing to produce mature neutrophils, immune cells vital for the clearance of bacteria from the body.
Based on this finding, the researchers then studied the role of another player in the immune system called toll-like receptor 4 (TLR4). TLRs are charged with the sentinel duty of detecting invading bacteria and sending signals to warn the immune system. As part of a healthy immune response, TLR4 activates two signaling pathways that lead to the production of neutrophils during an infection. During massive bacterial infections, two different molecules downstream of TLR4 prevent proper signaling, leaving TLR4 and the associated molecules responsible for inhibiting neutrophil production as well as damage to hematopoietic stem cells in the bone marrow.
What scientists learned from this study and what we can take away is this: the immune system is far from perfect. Even so, identifying and understanding when and how it falls short allows researchers to step in and improve the natural process with tools in modern medicine.
This study was published in the journal Stem Cell Reports.
Sources: Indiana University