Neutrophils, monocytes, and macrophages are white blood cells that act as scavengers of dead cells and foreign bodies such as bacteria and other pathogens. They move from the blood to the site of infection to mop up the disease-causing foreign matter.
However, in uncontrolled and severe infection, commonly called 'sepsis', there is abnormal activation and localisation of these immune cells.
As a result, these cells form ensembles, move around the body, and get deposited in important organs such as the lung, kidney, and liver, which could lead to multi-organ failure or even death.
"Given the importance of monocytes, macrophages, and neutrophils in sepsis, it is important to understand the mechanism of the migration of such cells to detect the stages of inflammation and sepsis," said Prof. Pranita P. Sarangi, Department of Biosciences and Bioengineering, IIT Roorkee, in a statement on Friday.
When these immune cells travel from the blood vessels through tissue spaces to reach the infected/inflamed site, they bind to proteins such as collagen or fibronectin.
This binding occurs via receptor molecules called integrins that are present on the cell surfaces. The integrin receptors enable communication between the immune cells and the surrounding matrix, which helps in cell migration and modulation of other functions.
However, their over-activity (called hyper-activation), can result in problems.
In the study, the team used two mouse models of sepsis to show the role of integrins in sepsis. When there is an infection, monocytes move from blood circulation and bone marrow towards the infected/inflamed tissue.
Once inside the tissues, these monocytes further mature into macrophages and by sensing the signals from the septic environment, these cells gradually switch their functions from inflammatory to immunosuppressive subtype that correlate with their integrin expression profile.
"These findings will help in detecting the stages of sepsis and appropriate treatment," said lead researcher Shiba Prasad Dash, doctoral student at the varsity.
The findings have been published in The Journal of Immunology.