Innate Immune Deficiency of Extremely Premature Neonates Can Be Reversed by Interferon-γ

Abstract

Background Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants. Methodology/Principal Findings We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ. Conclusion/Significance Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero . Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.

The impact of respiratory viruses on lung health after preterm birth

“…However, these defences against pathogens are severely compromised in preterm infants [20]. Features of immaturity of innate immunity following preterm birth including a smaller pool of effector cells (neutrophils, monocytes, natural killer cells and antigen presenting cells) and lower levels of inflammatory cytokines have been reported by several studies [18,21,22]. In addition, the levels of antigen specific immunoglobulins are substantially reduced in preterm infants, since these antibodies are largely transferred across the placenta during the third trimester, particularly after the 32nd week of gestation [23].…”

Recent Developments and Current Issues in the Epidemiology, Diagnosis, and Management of Bacterial and Fungal Neonatal Sepsis

“…As the fetal immune response begins at 24 weeks of age and development occurs until term, premature neonates do not benefit from complete immune system development, making them more susceptible to infection with organisms that term infants may be able to suppress. 1 …”

Innate Immunity and Human Milk MicroRNAs Content: A New Perspective for Premature Newborns

“…In the first three months of life, neonate's immunologic competence progresses rapidly as the cells of adaptive immunity mature acquiring the antigenic experience. In these 3 months of life, the neonate principally depends on components of the innate immune system, (7,8) yet, neonatal innate immune responses may not be fully developed so that the entire performance of its immune system is decreased (9). In premature neonates, the reduced pool of neutrophils and monocytes as well as their precursors lead to greater susceptibility to serious bacterial, viral or fungal infections.…”