The TLR-specific adjuvants R-848 and CpG-B endorse the immunological reaction of neonatal antigen-presenting cells

Schüller, Simone; Wisgrill, Lukas; Sadeghi, Kambis; Gindl, Erich; Helmer, Hanns; Husslein, Peter; Berger, Angelika; Spittler, Andreas; Förster-Waldl, Elisabeth

doi:10.1038/pr.2016.71

Cited by 13 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are fewer reports on the expression of T cell costimulation molecules (CD40, CD80, and CD86) by preterm monocytes, and these are also inconsistent [64,77,47]. Surface expression of adhesion molecules (CD11c, CD11b, and CD18) required for monocyte migration from the periphery into inflamed tissues has generally been reported as significantly reduced on preterm monocytes (Table 5).…”

Section: Surface Expression Of Antigen Presentation and Adhesion Molementioning

confidence: 99%

The phenotype and function of preterm infant monocytes: implications for susceptibility to infection

Jong

Strunk

Burgner

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells. Relatively little is known about these cells in preterm infants, especially about how their phenotype adapts to changes in the microbial environment during the immediate postnatal period. Overall, preterm monocytes exhibit attenuated proinflammatory cytokine responses following stimulation by whole bacterial or specific microbial components in vitro. These attenuated cytokine responses cannot be explained by a lack of intracellular signaling events downstream of pattern recognition receptors. This hyporesponsiveness also contrasts with mature, term-like phagocytosis capabilities detectable even in the most premature infant. Finally, human data on the effects of fetal chorioamnionitis on monocyte biology are incomplete and inconsistent. In this review, we present an integrated view of human studies focused on monocyte functions in preterm infants. We discuss how a developmental immaturity of these cells may contribute to preterm infants' susceptibility to infections.

show abstract

Section: Surface Expression Of Antigen Presentation and Adhesion Molementioning

confidence: 99%

The phenotype and function of preterm infant monocytes: implications for susceptibility to infection

Jong

Strunk

Burgner

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Studies investigating chemokine receptor expression and associated activation of preterm leukocytes are missing. In the context of immaturity, it has been shown that the LPSmediated activation of neonatal monocytes as well as neutrophils is diminished in preterm and term cord blood, affecting several immunological functions of those cells, which might explain the insufficient response of neonatal monocytes and neutrophils towards attracting chemokines (15,20,21). In our study, secretion of CXCL10 was significantly upregulated with increasing concentrations of TNF only in term infants.…”

Section: Discussionmentioning

confidence: 47%

Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundEndothelial cells (ECs) exert immunological functions such as production of proinflammatory cytokines/chemokines as well as facilitation of extravasation of immune cells into infected tissue. Limited data are available on the functionality of ECs from extremely preterm neonates during infection. Accordingly, the aim of our study was to investigate the immune response of premature ECs after proinflammatory stimulation.MethodsCell adhesion receptors' expression and function, nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) signaling, and chemokine production were analyzed in umbilical cord ECs from extremely preterm and term neonates after proinflammatory stimulation.ResultsP-selectin and E-selectin surface expression as well as NFκB signaling were lower after lipopolysaccharide (LPS) stimulation in premature ECs. Preterm ECs exhibited lower, but significant, cell-adhesive functions after LPS stimulation compared with term ECs. CCL2/CXCL8 chemokine secretion was significantly upregulated after proinflammatory stimulation in both groups. CXCL10 production was significantly increased in term but not in preterm ECs upon stimulation with tumor necrosis factor compared with unstimulated ECs.ConclusionExtremely premature ECs showed partly reduced expression levels and function of cell adhesion molecules. Both NFκB signaling and chemokine/cytokine production were reduced in premature ECs. The diminished endothelial proinflammatory immune response might result in impaired infection control of preterm newborns rendering them prone to severe infection.

show abstract

“…Recently, several reports described the immunomodulatory effect of IL‐29 on the enhancement of IFN‐α production in human pDCs . In our previous studies, we had demonstrated that pDCs from term and preterm neonates exhibit diminished IFN‐α production and decreased expression of activation markers after TLR‐specific triggers, which is thought to contribute to the susceptibility toward viral infections in neonates . Now, for the first time, we analyzed the production as well as the immunomodulatory effects of IL‐29 on adult and neonatal PBMC and pDCs.…”

Section: Discussionmentioning

confidence: 96%

“…This “immaturity” of neonatal immune responses is associated with neonatal morbidity and mortality . In recent years, novel insights in immunological impairments of the neonatal immune system have been described, revealing diminished defending responses against infectious triggers …”

Section: Introductionmentioning

confidence: 99%

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Wisgrill

Wessely

Netzl

et al. 2019

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.

show abstract

The TLR-specific adjuvants R-848 and CpG-B endorse the immunological reaction of neonatal antigen-presenting cells

Cited by 13 publications

References 34 publications

The phenotype and function of preterm infant monocytes: implications for susceptibility to infection

The phenotype and function of preterm infant monocytes: implications for susceptibility to infection

Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Contact Info

Product

Resources

About