IIT Roorkee researchers identify the role of WBC cell markers in sepsis-related complications

Roorkee: Researchers at the Indian Institute of Technology Roorkee, led by Prof. Pranita P Sarangi, Department of Biosciences and Bioengineering, IIT Roorkee, have shown the role of specific immune cell markers on the outcomes of severe infection and sepsis. This study, funded by the BioCARe Women Scientist grant and Innovative Young Biotechnologist Award grant from the Department of Biotechnology, GoI, has provided important insights into the role of immune cell markers on sepsis-related complications.

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 an infection to mop up the disease-causing foreign matter. However, in uncontrolled and severe infection, commonly called ‘sepsis’, there is abnormal activation and localization 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.

Speaking about her research, Prof. Pranita P Sarangi, Department of Biosciences and Bioengineering, IIT Roorkee, said, “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.”

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 this study, Prof. Sarangi’s group 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 the lead researcher,” said the lead researcher Mr. Shiba Prasad Dash, who is currently perusing his PhD under the guidance of Prof. Sarangi.

Talking about the research Prof. Ajit K Chaturvedi, Director IIT Roorkee said “The work advances the current understanding of sepsis biology and may be helpful in the development of therapeutics against this life-threatening condition.”

Results from this research work have been published in The Journal of Immunology,  the official journal of the American Association of Immunologists (AAI) and presented at the international conferences organized by the Indian Immunology Society (Immunocon-2019)