Major infections such as influenza and bacterial sepsis kill millions of people each year, often resulting from dangerous complications that impair blood vessels.

‘Variations in the Tie2 gene, which is expressed on the inner surface of blood vessels, play an important role in patient responses against infections such as influenza and bacterial sepsis.’

Senior author Samir Parikh, an investigator in BIDMC's CVBR and Division of Nephrology and Associate Professor of Medicine at Harvard Medical School, said, "The complications arising from sepsis and other infections can appear rapidly and dramatically, leaving patients in absolutely terrible shape. Patients might arrive at the hospital feeling generally unwell and within a few hours, can be in critical condition. But, this is not the case for everyone: many other patients arrive at the hospital with the same infectious symptoms, but get no worse and go on to recover fully." 




In studying the host response to infections, researchers have for many years focused on the role of the innate immune system. More recently, the focus has broadened to include the role played by the body's vascular system.
Parikh explained, "Improperly functioning blood vessels can have lethal consequences. For example, when the lungs' small blood vessels become leaky, the lungs fill with water and stop working properly, resulting in an often fatal condition called acute respiratory distress syndrome [ARDS]. No matter what type of infection a patient has initially, if he or she goes on to develop vascular leakage, that patient is in trouble. We wanted to find out if the Tie2 protein played a role in determining whether or not patients experience these devastating vascular complications."
The authors first determined in mouse models of several infections - including the parasitic infection malaria, the viral infection influenza and the bacterial infection sepsis - that all animals had decreased levels of Tie2 compared to baseline levels. Subsequent experiments revealed that reduced Tie2 was indeed setting the stage for vascular leakage and ensuing clinical complications in the animal models.
Corresponding author Chandra Ghosh, a member of the Parikh laboratory at BIDMC, said, "The Tie2 gene is essential for embryonic development and knockout mice without the Tie2 gene die in utero. Interestingly, mice with a single copy of the gene behave normally until they are challenged with infections."
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Parikh said, "This discovery was exciting. It was an exact match with the variants we had just identified in the genomic analysis. It supported our hypothesis that greater amounts of Tie2 protein may help people handle the stress of infection, while less-than-normal amounts of the protein leave individuals vulnerable to these dangerous complications."
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Source-Eurekalert