TLR expression, phagocytosis and oxidative burst in healthy and septic newborns in response to Gram-negative and Gram-positive rods

Abstract

The objective was to investigate whether phagocytes from healthy and septic newborns have a developmental deficiency in their capacity to recognize, phagocytize and generate hydrogen peroxide (H2O2) in response to Escherichia coli and Staphylococcus aureus. TLR expression and phagocytic ability of neutrophils and monocytes from 44 healthy preterm and term neonates, from 13 newborns with late onset sepsis and from 24 healthy adults were determined using flow cytometry, and H2O2 production was measured by dihydrorhodamine test. TLR-2 and TLR-4 expressions were similar among the groups. The phagocytic ability of monocytes and neutrophils exposed to E. coli and S. aureus in healthy and septic neonates was significantly reduced compared to that of adults. Monocytes from septic newborns exposed to E. coli had higher H2O2 production than those of the other groups. The oxidative burst of monocytes exposed to S. aureus was reduced in preterm newborns compared with term ones and those with sepsis, and no differences were found in the oxidative burst of neutrophils. Even with the ability to recognize bacteria, a decreased clearance of pathogens can cause an imbalance in the immune response, which could lead to a predisposition to sepsis. Once established, the increased production of cytokines and ROS in an attempt to control the infection as well as the lack of full phagocytic activity leads to persistence of the pathogen and a state of constant inflammation.