Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants

Gopalakrishna, Kathyayini P.; Macadangdang, Benjamin R; Rogers, Matthew B.; Tometich, Justin T.; Firek, Brian; Baker, Robyn; Ji, Junyi; Burr, Ansen H.P.; Ma, Congrong; Good, Misty; Morowitz, Michael J.; Hand, Timothy W.

doi:10.1038/s41591-019-0480-9

Cited by 227 publications

(204 citation statements)

References 46 publications

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“…Consistent with this hypothesis, an enhanced innate immune receptor expression and susceptibility to microbial ligands have been demonstrated in mouse fetal intestinal epithelium . The protective effect of breast milk has long been described; a recent study by Gopalakrishna et al now indicates that the lack of maternal IgA specific for the colonizing bacteria may contribute to the development of NEC . IgA may dampen the release of microbial stimuli and restrict access of bacteria to the tissue.…”

Section: Towards the Concept Of A Temporally Layered Postnatal Establmentioning

confidence: 80%

“…A recent investigation in humans demonstrated that it may contribute to the etiology of NEC. Expansion of Enterobacteriaceae that are not coated by maternal IgA precedes the onset of NEC . Further consequences could reach from autoimmune disorders due to interference with the induction of peripheral tolerance to failure to induce tolerance towards antigens that become available at weaning only.…”

Section: The Maturation Of the Adaptive Mucosal Immune Systemmentioning

confidence: 99%

“…Expansion of Enterobacteriaceae that are not coated by maternal IgA precedes the onset of NEC. 85 Further consequences could reach from autoimmune disorders due to interference with the induction of peripheral tolerance to failure to induce tolerance towards antigens that become available at weaning only. The clinical manifestations of this premature immune activation, however, might only become overt over time.…”

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

“…The concomitant transfer of maternal IgA antibodies directed against the very same set of bacteria may help to restrict bacterial colonization to the intestinal lumen and avoid inappropriate immune stimulation. 62,85,89 The rapid colonization by commensal bacteria and the low risk of infection because of breast milk being the sole food source may also allow the absence of antimicrobial mechanisms such as antimicrobial peptide-producing Paneth cells or epithelial TLR3 expression. 42,55 Still, the composition of the very early microbiota is highly individual because of the low colonization resistance.…”

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

“…34,40 The protective effect of breast milk has long been described; a recent study by Gopalakrishna et al now indicates that the lack of maternal IgA specific for the colonizing bacteria may contribute to the development of NEC. 85 IgA may dampen the release of microbial stimuli and restrict access of bacteria to the tissue. On the other hand, tumor necrosis factor secretion by fetal T lymphocytes and the relatively low abundance of intestinal Treg cells may promote inflammation upon barrier disruption.…”

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

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‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

Hornef

Torow

2019

Immunology

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Summary The intricate host–microbial interaction and the overwhelming complexity of the mucosal immune system in the adult host raise the question of how this system is initially established. Here, we propose the implementation of the concept of the ‘postnatal window of opportunity’ into the model of a ‘layered immunity’ to explain how the newborn's mucosal immune system matures and how host–microbial immune homeostasis is established after birth. We outline the concept of a timed succession of non‐redundant phases during postnatal immune development and discuss the possible influence of external factors and conditions.

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Section: Towards the Concept Of A Temporally Layered Postnatal Establmentioning

confidence: 80%

Section: The Maturation Of the Adaptive Mucosal Immune Systemmentioning

confidence: 99%

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

Section: Postnatal Maturation Of the Neonatal Innate Immune Systemmentioning

confidence: 99%

See 3 more Smart Citations

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

Hornef

Torow

2019

Immunology

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Respiratory Syncytial Virus Immunoreactivity, Vaccine Development, and Therapeutics

Elawar

Götte

Lee

et al. 2021

New Drug Development for Known and Emerging Viruses

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Developmental 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin exposure of either parent enhances the risk of necrotizing enterocolitis in neonatal mice

Mokshagundam

Ding

Rumph

et al. 2020

Birth Defects Research

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Background: Necrotizing enterocolitis (NEC) is a rare, but potentially fatal intestinal inflammatory condition most often arising in premature infants. Infants provided formula are also at greater risk of developing this disease. Although the majority of formula-fed, preterm infants do not develop NEC, up to 30% of infants with the disease do not survive. Thus, identifying additional, currently unrecognized factors, which may predispose a specific infant to NEC development would be a significant clinical advancement. In this regard, we have previously reported that offspring of female or male mice with a history of developmental exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit altered sensitivity to inflammatory challenges and are frequently born premature. Herein, we examined the possibility that, compared to unexposed mice (F1 NONE), developmental TCDD exposure of either parent (maternal, F1M TCDD , or paternal, F1P TCDD) would enhance the risk of NEC in offspring (F2 TCDD mice) in association with supplemental formula feeding. Methods: Beginning on postnatal day 7, all neonates were randomized to maternal milk only or maternal milk with up to 20 supplemental formula feedings. All pups remained with the Dams and were additionally allowed to nurse ad libitum. Results: Formula-fed F2 NONE pups rarely developed NEC while this disease was common in formula-fed F2M TCDD and F2P TCDD mice. Unexpectedly, 50% of F2M TCDD pups that were not provided supplemental formula also developed NEC. Conclusions: Our studies provide evidence that a history of parental TCDD exposure enhances the risk of NEC in offspring and suggest exposure to environmental immunotoxicants such as TCDD may also contribute to this inflammatory disease in humans.

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Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants

Cited by 227 publications

References 46 publications

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

Respiratory Syncytial Virus Immunoreactivity, Vaccine Development, and Therapeutics

Developmental 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin exposure of either parent enhances the risk of necrotizing enterocolitis in neonatal mice

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