Lactoferrin is a dynamic protein in human melioidosis and is a TLR4-dependent driver of TNF- release in Burkholderia thailandensis infection in vitro

摘要

Melioidosis is a severe tropical infection caused by the bacterium Burkholderia pseudomallei. Despite antibiotics, mortality in some regions remains very high, necessitating the need for alternative treatment strategies, including targeting the immune system. Lactoferrin is an iron-binding protein with a variety of different functions. In this study, we wanted to test whether lactoferrin alters how the immune system responds during melioidosis. To achieve this, we first tested the blood of melioidosis patients and found that patients who later died had higher lactoferrin levels compared to those who survived. We also stimulated blood obtained from healthy individuals with B. pseudomallei and found that lactoferrin levels increase. We next analyzed whether lactoferrin impaired how the bacteria grows and found that the growth of Burkholderia thailandensis, a closely related bacterium, was not affected by the addition of lactoferrin to the media. When human immune cells, called monocytes, were infected with B. thailandensis, we found that levels of a specific inflammatory protein, TNF-, increased after adding lactoferrin and that this effect was related to a specific immune recognition pathway called Toll-like receptor 4. These findings provide new data about the role of lactoferrin in modulating the immune response in melioidosis.