An Immunological Perspective on Neonatal Sepsis

Kan, Bernard; Razzaghian, Hamid Reza; Lavoie, Pascal M.

doi:10.1016/j.molmed.2016.02.001

Cited by 87 publications

(94 citation statements)

References 117 publications

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“…In contrast, estradiol, progesterone, adenosine, and prostaglandins circulate at high concentrations perinatally (42, 53–55) and provide a skewed anti-inflammatory milieu that preserves gestation and contributes to maintain tolerance to postnatal microbial colonization. Yet, this comes at the expense of weakening the ability to mount efficient immune responses against pathogens during the neonatal period (52, 56). Indeed, newborns are particularly susceptible to development of severe bacterial infections (57, 58).…”

Section: Discussionmentioning

confidence: 99%

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

et al. 2017

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Macrophage migration inhibitory factor (MIF) is a pleiotropic, constitutively expressed, pro-inflammatory cytokine and an important regulator of immune responses. d-dopachrome tautomerase (DDT), a newly described member of the MIF protein superfamily, shares sequence homology and biological activities with MIF. We recently reported that high expression levels of MIF sustain innate immune responses in newborns. Here, we elected to further characterize age-dependent MIF expression and to define whether DDT shares a similar expression profile with MIF. Therefore, we delineated the circulating concentrations of MIF and DDT throughout life using a large cohort of 307 subjects including fetuses, newborns, infants, children, and adults. Compared to levels measured in healthy adults (median: 5.7 ng/ml for MIF and 16.8 ng/ml for DDT), MIF and DDT plasma concentrations were higher in fetuses (median: 48.9 and 29.6 ng/ml), increased further at birth (median: 82.6 and 52.0 ng/ml), reached strikingly elevated levels on postnatal day 4 (median: 109.5 and 121.6 ng/ml), and decreased to adult levels during the first months of life. A strong correlation was observed between MIF and DDT concentrations in all age groups (R = 0.91, P < 0.0001). MIF and DDT levels correlated with concentrations of vascular endothelial growth factor, a protein upregulated under low oxygen tension and implicated in vascular and lung development (R = 0.70, P < 0.0001 for MIF and R = 0.65, P < 0.0001 for DDT). In very preterm infants, lower levels of MIF and DDT on postnatal day 6 were associated with an increased risk of developing bronchopulmonary dysplasia and late-onset neonatal sepsis. Thus, MIF and DDT plasma levels show a highly specific developmental profile in early life, supporting an important role for these cytokines during the neonatal period.

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Section: Discussionmentioning

confidence: 99%

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

et al. 2017

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“…When dysfunctional, these mechanisms reflect and contribute to pregnancy-related pathologies including pre-eclampsia, chorioamnionitis, and preterm labor (4,42). Our efforts are directed towards building a detailed and interactive data repository to characterize the normal cellular and functional organization of the fetal and maternal immune systems.…”

Section: Discussionmentioning

confidence: 99%

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy

Fragiadakis

Baca

Gherardini

et al. 2016

The Journal of Immunology

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Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus are critical for the maintenance of pregnancy and the delivery of an immuno-competent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyper-responsiveness of CD4+ and CD8+ T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPKAPK2, rpS6, and CREB phosphorylation in fetal Tbet+CD4+ T cells, CD8+ T cells, B cells and CD56loCD16+ NK cells and decreased ERK1/2, MAPKAPK2, and STAT1 phosphorylation in fetal intermediate and non-classical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.

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“…(4, 5)]. These maturational changes are likely to play an important role in preterm infants’ increased vulnerability to infections.…”

Section: Innate Immune Responsesmentioning

confidence: 99%

Antifungal Immunological Defenses in Newborns

2017

Self Cite

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Newborns are prone to fungal infections, largely due to Candida species. The immunological basis for this vulnerability is not yet fully understood. However, useful insights can be gained from the knowledge of the maturation of immune pathways during ontogeny, particularly when placed in context with how rare genetic mutations in humans predispose to fungal diseases. In this article, we review these most current data on immune functions in human newborns, highlighting pathways most relevant to the response to Candida. While discussing these data, we propose a framework of why deficiencies in these pathways make newborns particularly vulnerable to this opportunistic pathogen.

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An Immunological Perspective on Neonatal Sepsis

Cited by 87 publications

References 117 publications

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy

Antifungal Immunological Defenses in Newborns

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