Innate and adaptive immunity in necrotizing enterocolitis
Introduction
The onset of necrotizing enterocolitis (NEC) is thought to be affected by three primary factors: prematurity, formula feeding, and unbalanced microbial colonization of the intestine [1,2]. However, a prevalent unifying hypothesis has proposed that the preterm gut environment is highly sensitive to postnatal colonization with potentially pathogenic bacteria, which elicits inappropriate immune responses supporting NEC development [2]. Accordingly, abundant studies indicate that both innate and adaptive immune systems contribute to NEC pathology. By reviewing the functions of multiple components of the innate and adaptive immune systems in the neonatal intestine, we aim to provide a comprehensive understanding of the role of the immune system in NEC development.
Section snippets
Physical barrier of the intestine
The intestinal epithelium is composed of a complex network with approximately seven different cell types working together to balance the multiple functions of the small intestine, including nutrient absorption, antigen recognition, maintenance of mucosal integrity, and protection from micro-organisms. These cell types are joined by tight junctions and form a crypt-villus structure characteristic of the small intestine [3]. The villus is covered with enterocytes, goblet, enteroendocrine, and
Macrophages
Macrophages are important effector cells that contribute to the maintenance of homeostasis as well as initiating an immune response during injury. Intestinal macrophages typically reside beneath the epithelial layer in the lamina propria, where they are activated upon exposure to LPS and IFN-γ and respond by releasing pro-inflammatory cytokines and nitric oxide [53]. However, macrophage activation is amplified in the immature intestine, but is downregulated by tumor growth factor-β (TGF-β)
Conclusions
The complex pathogenesis of NEC has yet to be completely elucidated, and, at least regarding the role of adaptive immunity in NEC, more studies evaluating the differences between NEC in animal models and human infants are needed. However, recent discoveries have resulted in obtaining a more comprehensive understanding of intestinal immunology in the premature gut, such as the delicate interplay between the intestinal epithelium, commensal bacteria, molecular signaling, and innate and adaptive
Conflicts of interest
None declared.
Funding sources
M.G. is supported by grants K08DK101608 and R03DK111473 from the National Institutes of Health, March of Dimes Foundation Grant No. 5-FY17-79, and the Children's Discovery Institute of Washington University and St. Louis Children's Hospital.
Acknowledgment
We apologize to the authors whose work we were not able to include due to space limitations.
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