REVIEW ARTICLE The gut mucosal immune system in the neonatal period A. J. Battersby 1 & D. L. Gibbons 2,3 1 Academic Department of Paediatrics, Imperial College London, London, UK; 2 Peter Gorer Department of Immunobiology, King’s College London, London, UK; 3 National Institute for Health Research, Biomedical Research Centre, King’s Health Partners, Guy’s Hospital, London, UK To cite this article: Battersby AJ, Gibbons DL. The gut mucosal immune system in the neonatal period. Pediatr Allergy Immunol 2013: 00. Keywords neonate; neonatal; immune; immunity; infant; gut; intestine; intestinal; mucosa; mucosal Correspondence Dr Anna Battersby, Academic Department of Paediatrics, Wright-Fleming Building, St Mary’s Campus, Imperial College London, W2 1NY Tel.: 0207 594 3179 Fax: 0207 594 3984 E-mail: a.battersby@imperial.ac.uk Accepted for publication 26 March 2013 DOI:10.1111/pai.12079 Abstract Invasive sepsis in the newborn period is a major cause of childhood morbidity and mortality worldwide. The infant immune system undoubtedly differs intrinsically from the mature adult immune system. Current understanding is that the newborn infant immune system displays a range of competencies and is developing rather than deficient. The infant gut mucosal immune system is complex and displays a plethora of phenotypic and functional irregularities that may be clinically important. Various factors affect and modulate the infant gut mucosal immune system: components of the intestinal barrier, the infant gut microbiome, nutrition and the maternal–infant hybrid immune system. Elucidation of the phenotypic distribution of immune cells, their functional significance and the mucosa-specific pathways used by these cells is essential to the future of research in the field of infant immunology. Newborn infants and in particular those born preterm are highly susceptible to invasive and often overwhelming sepsis. Recent data from the World Health Organisation (WHO) suggest that worldwide every year 1.1 million neonates die from infection: including invasive sepsis, diarrhoeal disease and tetanus (1). In the UK, sepsis remains a major cause of morbidity and mortality for very low birthweight and preterm infants (2), yet the functional status of their immune system is not clearly defined. Why some neonates are able to adequately protect themselves against infection whilst others are not is a question that remains unanswered. At delivery, the newborn infant emerges from the sterile maternal intrauterine environment and the inexperienced immune system must adapt to a new world populated with a vast array of microorganisms: some friends and some foes. In the early neonatal period, the infant profits from a ‘hybrid’ maternal–infant immune system. Maternal factors play a crucial role as both an immediate aid to immune defence as well as in the development of the infant’s own adaptive immunity. The mucosal immune system is one of the first barriers to infection, and the gut mucosal immune system plays a critically important role. In this review, the complexities of the infant gut mucosal immune system are explored together with the various factors that modulate its function (Fig. 1). Due to the paucity of literature on human neonatal immune function, many of the theories discussed here are based on infant animal research or adult human models of gut immunity, both of which have their disadvantages. The infant gut mucosal immune system is likely to resemble the systemic immune system in some respects, that is, not wholly immature but exhibiting a wide-ranging func- tional capacity with some evidence of adult competencies (3). This range of responsiveness in the human infant may be dependent on the existence of a combination of immunogenic cells derived from separate haemopoietic lineages: foetal and adult. It has been hypothesized that the foetal T-lymphocyte (T cell) compartment is not just an immature version of the adult, but one derived from a separate lineage poised to deliver a tolerogenic response to antigens encountered in utero (4). Intrinsic characteristics of the infant gut mucosal immune system The exact composition of immune cells in the normal human infant gut remains ill-defined, particularly as normal infant intestinal tissue is difficult to obtain for research (5). However, from adults, we know that immunological tissue is distributed through the gut in three main compartments: the epithelium, the lamina propria and within Peyer’s patches (Fig. 2). T cells appear in the human foetal intestine as early as 11 weeks gestation and begin to form Peyer’s patches with B-lymphocyte (B cell) by 16 weeks gestation (6). ª 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd 1 Pediatric Allergy and Immunology