Immunity in Compromised Newborns

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Background

The risk of infection-related morbidities and mortality is particularly high in the newborn period. Before birth, the mammalian fetus is normally protected from adverse effects of environmental microbes and can gradually develop its immune competence in a relatively immunosuppressed condition. This situation changes dramatically at birth when rapid adaptation of the innate and adaptive immune systems is required to facilitate bacterial tolerance at epithelial surfaces and combat pathogens. A proper interaction between systemic immunity and immunity at epithelial surfaces (e.g. gut, lungs, skin) is required to prevent excessive epithelial inflammation, infections and bacterial translocation across immature barriers.

Prevention of neonatal infection and inflammation is a global challenge and particularly important for compromised newborns, such as those born preterm, growth-restricted or exposed to infections, dysmetabolism or other insults around birth. Specifically for the large group of very preterm infants (<80% gestation, about 2% of all infants), having very immature organs, neonatal bacteremia and sepsis, and inflammatory conditions in the lungs (e.g. bronchopulmonary dysplasia (BPD), gut (e.g. necrotizing enterocoilitis, NEC) and brain (white matter damage, WMD) are common. These infants may experience systemic immune suppression and a disrupted balance between microbiota establishment and mucosal immunity development. Further, a permeable blood-brain barrier may allow transfer of bacterial products from the circulation to brain regions, leading to neuroinflammation. Thus, NEC is characterized by excessive gut inflammatory responses with potential hyper-activation of both innate and adaptive immunity, including neutrophil extracellular traps, Th1 and Th17 pathways. However, it remains unclear how to stimulate immunity in such immune-compromised infants to avoid infections and inflammation. Well-controlled studies in animal models and systems level analysis in human infants are required to study the interacting effects of many factors involved in developmental immunity across mammals. Comprehensive and integrated analysis of biological material by novel -omics analytical technology may provide a new level of understanding to help describe, diagnose, treat and predict immune-related problems.

This collection of articles represents a combined effort from basic scientists and clinicians to indicate how immunity develops in the compromised newborn infant and in relevant animal models. A series of medical, microbial and diet interventions affect immune development in the blood, gut and brain. As an example, colostrum ingestion just after birth not only facilitates intestinal maturation, but stimulates systemic immunity to protect against infection and infection-related brain-injuries. Optimal nutrition and gut microbiota colonization may also be vital to secure immune-metabolic pathways along epithelia and in the blood to mount a sufficient inflammatory response following exposure to bacteria. Despite these challenges, compromised newborn mammals, when provided optimal clinical care, have a surprisingly high capacity to adapt their innate and adaptive immune systems to combat bacterial infections.

For this Research Topic, we aim to provide an overview of recent progress in our understanding of immunity in compromised newborns. The topic will highlight research related to the NEOMUNE research platform (2013-2019), a multinational research project based in Copenhagen, Denmark (www.neomune.ku.dk), but is not limited to research from this context. In vitro, animal and clinical studies with medical or dietary interventions, demonstrating effects on systemic or mucosal immunity, are welcome. Further, there is attention to the use of omics technologies and systems analysis to analyze varied biological samples from newborn infants and animals. The submission of Reviews, Mini-Reviews, Original Research, or Clinical Trial articles can cover, but are not limited to, the following topics:

1. Mechanistic or clinical development of systemic immunity in normal and compromised newborns (e.g. preterm, growth-restricted or other pre- or postnatal complications).
2. Mechanistic or clinical development of immunity in organs known to play a role for inflammatory conditions in compromised newborns (e.g. the gut, liver, lungs, skin, brain).
3. Dietary, medical, pharmacological or other therapies to prevent infections and inflammatory conditions in compromised newborn infants, animals, or animal models of infants.
4. Use of novel omics analytical tools (e.g. genomics, transcriptomics, epigenomics, proteomics, metabolomics, microbiomics) to characterize biological samples related to immunity in newborns.

Keywords: Fetus, Newborn, Infection, Sepsis, Immunity, Necrotizing Enterocolitis, Milk, Microbiota

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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