Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation

Strunk, Tobias; Prosser, Amy; Levy, Ofer; Philbin, Victoria J.; Simmer, Karen; Doherty, Dorota; Charles, Adrian; Richmond, Peter; Burgner, David; Currie, Andrew

doi:10.1038/pr.2012.48

Cited by 57 publications

(50 citation statements)

References 45 publications

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“…The higher phagocytic potential in preterm infants observed in our study has also been previously reported for phagocytosis of EC by monocytes and GBS by neutrophils (12,24). By contrast, other studies and our own previous data have described reduced or equivalent phagocytic potential of neutrophils and monocytes from preterm and term infants for EC, SE, or GBS (22,24,25). These discrepant data are most likely due to methodological differences in assessing phagocytosis.…”

Section: Phagocytosis In Newborn Whole Bloodcontrasting

confidence: 56%

“…Newborns, particularly preterm infants, have decreased levels and function of complement pathways (9,10,40). Phagocytosis of GBS, SE, and EC by isolated phagocytes has been shown to increase with, or be complement-dependent (25,41,42). However, in the presence of native complement in whole blood, we have shown that complement from preterm infants is not deficient or functionally defective for the uptake of SE and SA.…”

Section: Phagocytosis In Newborn Whole Bloodmentioning

confidence: 67%

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Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

et al. 2013

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Section: Phagocytosis In Newborn Whole Bloodcontrasting

confidence: 56%

Section: Phagocytosis In Newborn Whole Bloodmentioning

confidence: 67%

Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

et al. 2013

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“…Antimicrobial immune recognition and antigen presentation are also significantly impaired at this gestation even in "classical" high CD14-expressing monocytes, because of reduced receptor expression and intracellular signaling [9,10]. In fact, below 20-24 weeks of gestation, our data suggest little activity in extracellular PRR although this gestational age group was not included in studies [11][12][13][14][15]. By comparison, PRR activity in mononuclear cells increases until about 33 weeks of gestation, with the earliest activity detected in endosomal (TLR7, 8 and 9) and intracellular (e.g.…”

Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning

confidence: 56%

An Immunological Perspective on Neonatal Sepsis

Kan

Razzaghian

Lavoie

2016

Trends in Molecular Medicine

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Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis.

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“…However, because TLR-dependent cytokine responses generally correlate poorly with their corresponding receptor gene or protein expression, it is important to validate the impact of a reduced expression of PRR at the functional level by examining relevant cytokine responses (6). Others reported that endotoxin (TLR4) responses in monocytes from preterm neonates born below 32 wk of gestation are already mature (i.e., comparable to responses measured at the full term of gestation) by the second week of age, although it remained unclear whether this is also true of infants born at the lower end of gestation (15).…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptors (TLRs) play a predominant role as a major family of PRR that act as essential "detectors" in the recognition of microbial pathogens by the innate immune system. We and others have shown that TLR-induced cytokine immune reactivity are profoundly attenuated in cord blood of very preterm neonates and develops asynchronously over the last trimester of gestation (6)(7)(8)(9)(10). These infants also display sustainably high levels of systemic inflammation, indicating a potential immune dysregulation that has also been associated with worsened clinical outcomes (11).…”

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confidence: 99%

Attenuated innate immune defenses in very premature neonates during the neonatal period

et al. 2015

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Background: Antimicrobial responses have been shown to be profoundly attenuated in very preterm neonates when examined on cord blood. However, we lack data on these responses at the time these neonates are most vulnerable to infections. Methods: Multiple cytokine responses to two prototypic Toll-like receptor (TLR) agonists: lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8) were prospectively measured in preterm neonates born ≤30 wk of gestation (n = 50) during the first 28 d of age using whole blood and single-cell multiparameter flow cytometry assays. Results were compared to term neonates (n = 30) and adult controls (n = 25). results: In preterm neonates, LPS and R848 responses remained attenuated in both cord blood and in the first 28 d of age. These responses showed significant maturation over time after adjusting for gestational age and were confirmed in monocytes and dendritic cells on a per-cell basis. We detected no major contribution of chorioamnionitis, maternal antenatal corticosteroids or magnesium sulfate treatment, labor, or mode of delivery to the maturation of cytokine responses. conclusion: Innate immune antimicrobial defenses are profoundly attenuated developmentally in very preterm neonates during the neonatal period, suggesting that exogenous factors drive the sustained systemic inflammation that has been linked to increased morbidities in these infants.d espite improvements in neonatal health care, mortality from infections has continued to increase in very preterm neonates over the last two decades, owing to the improved survival of smaller and more vulnerable infants (1). However, the underlying immunological basis of their high morbidities and high vulnerability to sepsis remains poorly understood (2). To defend themselves against infection, neonates rely on first-line, innate immune defense mechanisms. These mechanisms include the detection of specific microbial molecular structures called pathogenassociated molecular patterns through specialized receptors termed pattern recognition receptors (PRR), but also other defense mechanisms such as phagocytosis and antigen presentation to the adaptive immune system.It is widely stated that the high risk of neonatal sepsis observed in these infants is due to immature immune defense mechanisms. However, data are lacking on the development of immune functions beyond measures performed on umbilical cord blood. Recent studies have reported reduced antigen-presenting receptor expression during the first week of age in infants born below 33 wk of gestation (3,4). In contrast, phagocytic functions in these infants are more comparable to term infants (5). Toll-like receptors (TLRs) play a predominant role as a major family of PRR that act as essential "detectors" in the recognition of microbial pathogens by the innate immune system. We and others have shown that TLR-induced cytokine immune reactivity are profoundly attenuated in cord blood of very preterm neonates and develops asynchronously over the last trimester of gestation (6-10). These infants als...

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Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation

Cited by 57 publications

References 45 publications

Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

An Immunological Perspective on Neonatal Sepsis

Attenuated innate immune defenses in very premature neonates during the neonatal period

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